17-81985511-G-C

Variant names:

• chr17-81985511-G-C
• rs149772045
• NM_024083.4:c.278G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024083.4(ASPSCR1):​c.278G>C​(p.Arg93Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,256 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: ASPSCR1 NM_024083.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASPSCR1	NM_024083.4	c.278G>C	p.Arg93Pro	missense_variant	Exon 4 of 16	ENST00000306739.9	NP_076988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9	c.278G>C	p.Arg93Pro	missense_variant	Exon 4 of 16	1	NM_024083.4	ENSP00000302176.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152256 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Benign	0.78
DEOGEN2	Uncertain	0.63	.;.;D;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.69	D;D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.1	.;M;M;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.3	.;D;D;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.10	.;T;D;.;.
Sift4G	Uncertain	0.023	D;D;T;D;D
Polyphen		1.0, 1.0	.;D;D;.;D
Vest4		0.88, 0.87, 0.86, 0.85
MutPred		0.43		.;Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);.;
MVP		0.36
MPC		0.16
ClinPred		0.76	D
GERP RS		5.3
Varity_R		0.82
gMVP		0.84

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

Other links and lift over

dbSNP: rs149772045; hg19: chr17-79943387;