9-132897613-GAAAAAA-GAAAAAAAAAAAAA

Position:

• chr9-132897613-GAAAAAA-GAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000368.5(TSC1):​c.2626-10_2626-4dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000096 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSC1 NM_000368.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.517

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 9-132897613-G-GAAAAAAA is Benign according to our data. Variant chr9-132897613-G-GAAAAAAA is described in ClinVar as [Benign]. Clinvar id is 1692400.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC1	NM_000368.5	c.2626-10_2626-4dupTTTTTTT		splice_region_variant, intron_variant		ENST00000298552.9	NP_000359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC1	ENST00000298552.9	c.2626-10_2626-4dupTTTTTTT		splice_region_variant, intron_variant		1	NM_000368.5	ENSP00000298552.3
TSC1	ENST00000490179.4	c.2626-10_2626-4dupTTTTTTT		splice_region_variant, intron_variant		3		ENSP00000495533.2

Frequencies

GnomAD3 genomes AF: 0.00000960 AC: 1 AN: 104132 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000184

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000439 AC: 55 AN: 1253866 Hom.: 0 Cov.: 0 AF XY: 0.0000385 AC XY: 24 AN XY: 623200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000110

Gnomad4 ASJ exome AF: 0.0000495

Gnomad4 EAS exome AF: 0.0000846

Gnomad4 SAS exome AF: 0.0000914

Gnomad4 FIN exome AF: 0.0000603

Gnomad4 NFE exome AF: 0.0000395

Gnomad4 OTH exome AF: 0.0000193

GnomAD4 genome AF: 0.00000960 AC: 1 AN: 104132 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 48576

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000184

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

Aug 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5901000; hg19: chr9-135773000;