9-132897613-G-GAAAAAA

Position:

• chr9-132897613-G-GAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000298552.9(TSC1):​c.2626-4_2626-3insTTTTTT 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000029 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSC1 ENST00000298552.9 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC1	NM_000368.5	c.2626-4_2626-3insTTTTTT		splice_region_variant, splice_polypyrimidine_tract_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.2626-4_2626-3insTTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000368.5	ENSP00000298552	P4

Frequencies

GnomAD3 genomes AF: 0.0000288 AC: 3 AN: 104130 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000415

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: 0.0000367

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000152 AC: 190 AN: 1253650 Hom.: 1 Cov.: 0 AF XY: 0.000170 AC XY: 106 AN XY: 623064

Gnomad4 AFR exome AF: 0.0000709

Gnomad4 AMR exome AF: 0.000477

Gnomad4 ASJ exome AF: 0.000396

Gnomad4 EAS exome AF: 0.000451

Gnomad4 SAS exome AF: 0.000488

Gnomad4 FIN exome AF: 0.0000604

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.000174

GnomAD4 genome AF: 0.0000288 AC: 3 AN: 104130 Hom.: 1 Cov.: 0 AF XY: 0.0000617 AC XY: 3 AN XY: 48596

Gnomad4 AFR AF: 0.0000414

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: 0.0000367

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Sema4, Sema4

Apr 28, 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;