9-132924530-G-T

Position:

• chr9-132924530-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000368.5(TSC1):​c.364-1038C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,946 control chromosomes in the GnomAD database, including 36,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36577 hom., cov: 31)
• Consequence: TSC1 NM_000368.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC1	NM_000368.5	c.364-1038C>A		intron_variant		ENST00000298552.9	NP_000359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC1	ENST00000298552.9	c.364-1038C>A		intron_variant		1	NM_000368.5	ENSP00000298552.3
TSC1	ENST00000490179.4	c.364-1038C>A		intron_variant		3		ENSP00000495533.2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105249 AN: 151828 Hom.: 36539 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.693 AC: 105345 AN: 151946 Hom.: 36577 Cov.: 31 AF XY: 0.695 AC XY: 51562 AN XY: 74242

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.683

Alfa AF: 0.638 Hom.: 2061

Bravo AF: 0.684

Asia WGS AF: 0.718 AC: 2481 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.9
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13295634; hg19: chr9-135799917;