17-81983627-A-C

Position:

• chr17-81983627-A-C

Variant summary

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

The NM_024083.4(ASPSCR1):​c.232A>C​(p.Met78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ASPSCR1 NM_024083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41

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 (HGNC:):

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/exons	MANE	Protein	UniProt
ASPSCR1	NM_024083.4	c.232A>C	p.Met78Leu	missense_variant	3/16	ENST00000306739.9	NP_076988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPSCR1	ENST00000306739.9	c.232A>C	p.Met78Leu	missense_variant	3/16	1	NM_024083.4	ENSP00000302176.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2023

The c.232A>C (p.M78L) alteration is located in exon 3 (coding exon 3) of the ASPSCR1 gene. This alteration results from a A to C substitution at nucleotide position 232, causing the methionine (M) at amino acid position 78 to be replaced by a leucine (L). 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	0.38
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Uncertain	0.59	.;.;D;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	.;L;L;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.4	.;N;N;.;.
REVEL	Benign	0.29
Sift	Benign	0.058	.;T;T;.;.
Sift4G	Uncertain	0.051	T;T;T;T;T
Polyphen		0.80, 0.83	.;P;P;.;P
Vest4		0.68, 0.68, 0.66, 0.77
MutPred		0.47		.;Loss of disorder (P = 0.1508);Loss of disorder (P = 0.1508);Loss of disorder (P = 0.1508);.;
MVP		0.21
MPC		0.099
ClinPred		0.72	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79941503;