Variant chr9-132944745-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000644097.1(TSC1):c.-317C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 397,482 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 77 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 11 hom. )

Consequence

TSC1
ENST00000644097.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0900

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:

GFI1B (HGNC:4238): (growth factor independent 1B transcriptional repressor) This gene encodes a zinc-finger containing transcriptional regulator that is primarily expressed in cells of hematopoietic lineage. The encoded protein complexes with numerous other transcriptional regulatory proteins including GATA-1, runt-related transcription factor 1 and histone deacetylases to control expression of genes involved in the development and maturation of erythrocytes and megakaryocytes. Mutations in this gene are the cause of the autosomal dominant platelet disorder, platelet-type bleeding disorder-17. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

GFI1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 9-132944745-G-T is Benign according to our data. Variant chr9-132944745-G-T is described in ClinVar as [Benign]. Clinvar id is 1269155.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSC1	XM_011518979.3 linkuse as main transcript	c.-144+440C>A		intron_variant			XP_011517281.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	Appris
TSC1	ENST00000644097.1 linkuse as main transcript	c.-317C>A	5_prime_UTR_variant	1/23	ENSP00000494682	A1
TSC1	ENST00000643362.2 linkuse as main transcript	c.-144+2014C>A	intron_variant		ENSP00000496398
TSC1	ENST00000646440.2 linkuse as main transcript	c.-144+440C>A	intron_variant		ENSP00000495830	P4

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2505

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0564

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0119

GnomAD4 exome

AF:

0.00226

AC:

555

AN:

245134

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

241

AN XY:

124228

show subpopulations

Gnomad4 AFR exome

AF:

0.0555

Gnomad4 AMR exome

AF:

0.00527

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000826

Gnomad4 OTH exome

AF:

0.00644

GnomAD4 genome

AF:

0.0165

AC:

2521

AN:

152348

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1153

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0565

Gnomad4 AMR

AF:

0.00842

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00325

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.5

DANN

Benign

0.72

Splicing

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