dbSNP rs759144950: ASPSCR1:p.Asn18Asp (chr17-81977698-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_024083.4(ASPSCR1):c.52A>G(p.Asn18Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 1,366,878 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

ASPSCR1
NM_024083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

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:

LOC105371939 (HGNC:):

LOC105371939 links:

Genome browser will be placed here

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=0.14354718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPSCR1	NM_024083.4 link	c.52A>G	p.Asn18Asp	missense_variant	Exon 1 of 16	ENST00000306739.9	NP_076988.1	Q9BZE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9 link	c.52A>G	p.Asn18Asp	missense_variant	Exon 1 of 16	1	NM_024083.4	ENSP00000302176.4		Q9BZE9-1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000193

AC:

AN:

51698

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

31362

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000601

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000403

AC:

AN:

1215170

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

594578

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:

0.000695

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000123

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151708

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000153

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.52A>G (p.N18D) alteration is located in exon 1 (coding exon 1) of the ASPSCR1 gene. This alteration results from a A to G substitution at nucleotide position 52, causing the asparagine (N) at amino acid position 18 to be replaced by an aspartic acid (D). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Uncertain

0.56

.;D;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L;.

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.1

D;D;.

REVEL

Benign

0.089

Sift

Uncertain

0.015

D;D;.

Sift4G

Uncertain

0.024

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.36

MutPred

0.31

Loss of MoRF binding (P = 0.0396);Loss of MoRF binding (P = 0.0396);Loss of MoRF binding (P = 0.0396);

MVP

0.20

MPC

0.12

ClinPred

0.34

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.63

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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