Variant 17-81995996-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000306739.9(ASPSCR1):c.437C>T(p.Thr146Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,609,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

ASPSCR1
ENST00000306739.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

ASPSCR1 (HGNC:13825): (ASPSCR1 tether for SLC2A4, UBX domain containing) The protein encoded by this gene contains a UBX domain and interacts with glucose transporter type 4 (GLUT4). This protein is a tether, which sequesters the GLUT4 in intracellular vesicles in muscle and fat cells in the absence of insulin, and redistributes the GLUT4 to the plasma membrane within minutes of insulin stimulation. Translocation t(X;17)(p11;q25) of this gene with transcription factor TFE3 gene results in a ASPSCR1-TFE3 fusion protein in alveolar soft part sarcoma and in renal cell carcinomas. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Oct 2011]

ASPSCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010150164).

BP6

Variant 17-81995996-C-T is Benign according to our data. Variant chr17-81995996-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2356734.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPSCR1	NM_024083.4 linkuse as main transcript	c.437C>T	p.Thr146Met	missense_variant	6/16	ENST00000306739.9	NP_076988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9 linkuse as main transcript	c.437C>T	p.Thr146Met	missense_variant	6/16	1	NM_024083.4	ENSP00000302176	P2	Q9BZE9-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000190

AC:

AN:

236872

Hom.:

AF XY:

0.000186

AC XY:

AN XY:

128752

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00342

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000955

Gnomad OTH exome

AF:

0.000347

GnomAD4 exome

AF:

0.0000954

AC:

139

AN:

1457210

Hom.:

Cov.:

AF XY:

0.0000994

AC XY:

AN XY:

724596

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00323

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000158

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000518

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.27

.;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.75

T;T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

.;N;N;.

REVEL

Benign

0.028

Sift

Benign

0.30

.;T;T;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.025, 0.020, 0.11

.;B;B;B

Vest4

0.31, 0.32, 0.35

MVP

0.099

MPC

0.11

ClinPred

0.0063

GERP RS

1.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.012

gMVP

0.49

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