rs368146790

Variant names:

• chr17-81983601-A-C
• rs368146790
• NM_024083.4:c.206A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-81983601-A-C
• chr17-81983601-A-G

Variant summary

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

The NM_024083.4(ASPSCR1):​c.206A>C​(p.Asn69Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,664 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: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASPSCR1 NM_024083.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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.206A>C	p.Asn69Thr	missense_variant	Exon 3 of 16	ENST00000306739.9	NP_076988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9	c.206A>C	p.Asn69Thr	missense_variant	Exon 3 of 16	1	NM_024083.4	ENSP00000302176.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461664 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Uncertain	0.66	.;.;D;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	.;M;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.5	.;D;D;.
REVEL	Benign	0.23
Sift	Benign	0.071	.;T;T;.
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.61, 0.59, 0.57
MutPred		0.57		.;Gain of phosphorylation at N69 (P = 0.0809);Gain of phosphorylation at N69 (P = 0.0809);Gain of phosphorylation at N69 (P = 0.0809);
MVP		0.65
MPC		0.11
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.16
gMVP		0.36

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

Other links and lift over

dbSNP: rs368146790; hg19: chr17-79941477;