Variant chr11-18481759-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006292.4(TSG101):c.954C>T(p.Ile318=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,614,136 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 145 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 136 hom. )

Consequence

TSG101
NM_006292.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

TSG101 (HGNC:15971): (tumor susceptibility 101) The protein encoded by this gene belongs to a group of apparently inactive homologs of ubiquitin-conjugating enzymes. The gene product contains a coiled-coil domain that interacts with stathmin, a cytosolic phosphoprotein implicated in tumorigenesis. The protein may play a role in cell growth and differentiation and act as a negative growth regulator. In vitro steady-state expression of this tumor susceptibility gene appears to be important for maintenance of genomic stability and cell cycle regulation. Mutations and alternative splicing in this gene occur in high frequency in breast cancer and suggest that defects occur during breast cancer tumorigenesis and/or progression. [provided by RefSeq, Jul 2008]

TSG101 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 11-18481759-G-A is Benign according to our data. Variant chr11-18481759-G-A is described in ClinVar as [Benign]. Clinvar id is 774621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSG101	NM_006292.4 linkuse as main transcript	c.954C>T	p.Ile318=	synonymous_variant	9/10	ENST00000251968.4	NP_006283.1
TSG101	XM_005253108.5 linkuse as main transcript	c.798C>T	p.Ile266=	synonymous_variant	10/11		XP_005253165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSG101	ENST00000251968.4 linkuse as main transcript	c.954C>T	p.Ile318=	synonymous_variant	9/10	1	NM_006292.4	ENSP00000251968	P1	Q99816-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3626

AN:

152168

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0816

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000852

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00626

AC:

1573

AN:

251394

Hom.:

AF XY:

0.00449

AC XY:

610

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0797

Gnomad AMR exome

AF:

0.00529

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00275

AC:

4023

AN:

1461850

Hom.:

136

Cov.:

AF XY:

0.00243

AC XY:

1764

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0848

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000452

Gnomad4 OTH exome

AF:

0.00606

GnomAD4 genome

AF:

0.0238

AC:

3630

AN:

152286

Hom.:

145

Cov.:

AF XY:

0.0230

AC XY:

1710

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0815

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0275

Asia WGS

AF:

0.00520

AC:

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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