chr17-81983629-G-A

Variant names:

• chr17-81983629-G-A
• NM_024083.4:c.234G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001330528.2(ASPSCR1):​c.3G>A​(p.Met1?) variant causes a start lost change involving the alteration of a 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_001330528.2 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.70

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 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 14 codons. Genomic position: 81983666. Lost 0.027 part of the original CDS.
• 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.234G>A	p.Met78Ile	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.234G>A	p.Met78Ile	missense_variant	Exon 3 of 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

Feb 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.234G>A (p.M78I) 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 234, causing the methionine (M) at amino acid position 78 to be replaced by an isoleucine (I). 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	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.62	.;.;D;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.46	T;T;T;T;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L;L;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.2	.;D;D;.;.
REVEL	Benign	0.18
Sift	Benign	0.044	.;D;T;.;.
Sift4G	Benign	0.26	T;T;T;T;T
Polyphen		0.95, 0.96	.;P;D;.;P
Vest4		0.77, 0.77, 0.74, 0.77
MutPred		0.44		.;Gain of catalytic residue at P80 (P = 0.0305);Gain of catalytic residue at P80 (P = 0.0305);Gain of catalytic residue at P80 (P = 0.0305);.;
MVP		0.26
MPC		0.12
ClinPred		0.95	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.56

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: chr17-79941505;