9-132897612-T-TAA

Variant summary

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

The NM_000368.5(TSC1):c.2626-3_2626-2insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSC1 NM_000368.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.387

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 9-132897612-T-TAA is Benign according to our data. Variant chr9-132897612-T-TAA is described in ClinVar as [Benign]. Clinvar id is 466089.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC1	NM_000368.5	c.2626-3_2626-2insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000298552.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC1	ENST00000298552.9	c.2626-3_2626-2insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000368.5	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 112 AN: 43072 Hom.: 0 Cov.: 14 FAILED QC

Gnomad AFR AF: 0.000395

Gnomad AMI AF: 0.00870

Gnomad AMR AF: 0.00450

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.00272

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00423

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00249 AC: 2157 AN: 867672 Hom.: 0 Cov.: 27 AF XY: 0.00265 AC XY: 1156 AN XY: 436752

Gnomad4 AFR exome AF: 0.000808

Gnomad4 AMR exome AF: 0.00488

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.00273

Gnomad4 SAS exome AF: 0.0114

Gnomad4 FIN exome AF: 0.00376

Gnomad4 NFE exome AF: 0.00182

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00260 AC: 112 AN: 43112 Hom.: 0 Cov.: 14 AF XY: 0.00248 AC XY: 50 AN XY: 20132

Gnomad4 AFR AF: 0.000394

Gnomad4 AMR AF: 0.00449

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00523

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.00272

Gnomad4 NFE AF: 0.00423

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Tuberous sclerosis 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 16, 2021

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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: rs760737807; hg19: chr9-135772999; COSMIC: COSV53767000; COSMIC: COSV53767000;