Variant 17-81983649-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024083.4(ASPSCR1):c.254G>A(p.Arg85His) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,612,290 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: 𝑓 0.000073 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ASPSCR1
NM_024083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2446397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPSCR1	NM_024083.4 link	c.254G>A	p.Arg85His	missense_variant	3/16	ENST00000306739.9	NP_076988.1	Q9BZE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9 link	c.254G>A	p.Arg85His	missense_variant	3/16	1	NM_024083.4	ENSP00000302176.4		Q9BZE9-1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000483

AC:

AN:

248322

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

134516

show subpopulations

Gnomad AFR exome

AF:

0.0000628

Gnomad AMR exome

AF:

0.0000874

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000446

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1460644

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151646

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74052

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000495

AC:

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

Nov 09, 2024

The c.254G>A (p.R85H) alteration is located in exon 3 (coding exon 3) of the ASPSCR1 gene. This alteration results from a G to A substitution at nucleotide position 254, causing the arginine (R) at amino acid position 85 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.71

.;.;D;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.041

MetaRNN

Benign

0.24

T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.0

.;M;M;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.8

.;D;D;.;.

REVEL

Benign

0.099

Sift

Uncertain

0.0020

.;D;D;.;.

Sift4G

Uncertain

0.052

T;D;T;T;T

Polyphen

1.0, 1.0

.;D;D;.;D

Vest4

0.47, 0.47, 0.46, 0.46

MVP

0.34

MPC

0.13

ClinPred

0.62

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.24

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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