9-132897613-GAAAAAAAAAAAA-G

Variant names:

• chr9-132897613-GAAAAAAAAAAAA-G
• rs5901000
• NM_000368.5:c.2626-15_2626-4delTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000368.5(TSC1):​c.2626-15_2626-4delTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: TSC1 NM_000368.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

Genes affected

TSC1 (HGNC:12362): (TSC complex subunit 1) This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including TSC2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]

TSC1 Gene-Disease associations (from GenCC):

• tuberous sclerosis

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• tuberous sclerosis 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• lung lymphangioleiomyomatosis

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• tuberous sclerosis complex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 9-132897613-GAAAAAAAAAAAA-G is Benign according to our data. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-132897613-GAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2707227.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSC1	NM_000368.5	c.2626-15_2626-4delTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 20 of 22	ENST00000298552.9	NP_000359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSC1	ENST00000298552.9	c.2626-15_2626-4delTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 20 of 22	1	NM_000368.5	ENSP00000298552.3
TSC1	ENST00000490179.4	c.2626-15_2626-4delTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 21 of 23	3		ENSP00000495533.2

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Tuberous sclerosis 1 Benign:1

Jan 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5901000; hg19: chr9-135773000;