Variant 17-81979197-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024083.4(ASPSCR1):c.116C>T(p.Thr39Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ASPSCR1
NM_024083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

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:

ASPSCR1 (HGNC:):

ASPSCR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34660518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPSCR1	NM_024083.4 linkuse as main transcript	c.116C>T	p.Thr39Met	missense_variant	2/16	ENST00000306739.9	NP_076988.1	Q9BZE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9 linkuse as main transcript	c.116C>T	p.Thr39Met	missense_variant	2/16	1	NM_024083.4	ENSP00000302176.4		Q9BZE9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2023

The c.116C>T (p.T39M) alteration is located in exon 2 (coding exon 2) of the ASPSCR1 gene. This alteration results from a C to T substitution at nucleotide position 116, causing the threonine (T) at amino acid position 39 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

.;.;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;N;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

.;N;N;.

REVEL

Benign

0.23

Sift

Uncertain

0.013

.;D;D;.

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.

Vest4

0.68, 0.70, 0.64

MutPred

0.46

.;Gain of catalytic residue at V35 (P = 0.0245);Gain of catalytic residue at V35 (P = 0.0245);Gain of catalytic residue at V35 (P = 0.0245);

MVP

0.52

MPC

0.11

ClinPred

0.85

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.067

gMVP

0.44

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

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