rs79357051

Positions:

• chr16-2053829-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_000548.5(TSC2):​c.336+377T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00752 in 505,252 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0059 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (25 hom.)
• Consequence: TSC2 NM_000548.5 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.16

Genes affected

TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]

TSC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00587 (895/152348) while in subpopulation NFE AF= 0.00967 (658/68028). AF 95% confidence interval is 0.00906. There are 2 homozygotes in gnomad4. There are 382 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 895 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC2	NM_000548.5	c.336+377T>C		intron_variant		ENST00000219476.9	NP_000539.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC2	ENST00000219476.9	c.336+377T>C		intron_variant		5	NM_000548.5	ENSP00000219476.3

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 895 AN: 152230 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00967

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00708 AC: 898 AN: 126810 Hom.: 3 AF XY: 0.00717 AC XY: 497 AN XY: 69362

Gnomad AFR exome AF: 0.00164

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.00353

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00727

Gnomad FIN exome AF: 0.00170

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00824 AC: 2907 AN: 352904 Hom.: 25 Cov.: 0 AF XY: 0.00836 AC XY: 1645 AN XY: 196682

Gnomad4 AFR exome AF: 0.00215

Gnomad4 AMR exome AF: 0.00593

Gnomad4 ASJ exome AF: 0.00356

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00784

Gnomad4 FIN exome AF: 0.00191

Gnomad4 NFE exome AF: 0.00978

Gnomad4 OTH exome AF: 0.00933

GnomAD4 genome AF: 0.00587 AC: 895 AN: 152348 Hom.: 2 Cov.: 33 AF XY: 0.00513 AC XY: 382 AN XY: 74486

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00555

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00967

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00766 Hom.: 1

Bravo AF: 0.00659

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs79357051; hg19: chr16-2103830;