Variant chr9-132900647-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000368.5(TSC1):c.2625+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,607,722 control chromosomes in the GnomAD database, including 192,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13705 hom., cov: 32)

Exomes 𝑓: 0.49 ( 178315 hom. )

Consequence

TSC1
NM_000368.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.156

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-132900647-C-T is Benign according to our data. Variant chr9-132900647-C-T is described in ClinVar as [Benign]. Clinvar id is 670691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132900647-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSC1	NM_000368.5 linkuse as main transcript	c.2625+68G>A		intron_variant		ENST00000298552.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSC1	ENST00000298552.9 linkuse as main transcript	c.2625+68G>A		intron_variant		1	NM_000368.5	P4	Q92574-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58803

AN:

151956

Hom.:

13705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.398

GnomAD4 exome

AF:

0.489

AC:

711944

AN:

1455648

Hom.:

178315

Cov.:

AF XY:

0.493

AC XY:

357077

AN XY:

724162

show subpopulations

Gnomad4 AFR exome

AF:

0.0971

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.588

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.387

AC:

58803

AN:

152074

Hom.:

13705

Cov.:

AF XY:

0.396

AC XY:

29457

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.552

Gnomad4 SAS

AF:

0.603

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.483

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.467

Hom.:

22157

Bravo

AF:

0.359

Asia WGS

AF:

0.536

AC:

1860

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 66% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 61. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over