Variant chr9-132906639-C-A 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.1438+92G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,137,450 control chromosomes in the GnomAD database, including 12,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1974 hom., cov: 32)

Exomes 𝑓: 0.14 ( 10634 hom. )

Consequence

TSC1
NM_000368.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.12

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=-0.93).

BP6

Variant 9-132906639-C-A is Benign according to our data. Variant chr9-132906639-C-A is described in ClinVar as [Benign]. Clinvar id is 1291082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC1	NM_000368.5 linkuse as main transcript	c.1438+92G>T		intron_variant		ENST00000298552.9	NP_000359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSC1	ENST00000298552.9 linkuse as main transcript	c.1438+92G>T		intron_variant		1	NM_000368.5	ENSP00000298552	P4	Q92574-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23765

AN:

151878

Hom.:

1964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.0853

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.143

AC:

140889

AN:

985476

Hom.:

10634

Cov.:

AF XY:

0.141

AC XY:

70841

AN XY:

503362

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0940

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.0689

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.157

AC:

23805

AN:

151974

Hom.:

1974

Cov.:

AF XY:

0.151

AC XY:

11215

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.0855

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.163

Hom.:

345

Bravo

AF:

0.159

Asia WGS

AF:

0.130

AC:

452

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.4

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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