chr17-81996013-C-G

Variant names:

• chr17-81996013-C-G
• rs368561373
• NM_024083.4:c.454C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024083.4(ASPSCR1):​c.454C>G​(p.Arg152Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000596 in 1,610,024 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000063 (2 hom.)
• Consequence: ASPSCR1 NM_024083.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050058126).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPSCR1	NM_024083.4	MANE Select	c.454C>G	p.Arg152Gly	missense	Exon 6 of 16	NP_076988.1	Q9BZE9-1
	ASPSCR1	NM_001251888.2		c.454C>G	p.Arg152Gly	missense	Exon 6 of 17	NP_001238817.1	Q9BZE9-2
	ASPSCR1	NM_001330528.2		c.223C>G	p.Arg75Gly	missense	Exon 5 of 15	NP_001317457.1	Q9BZE9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPSCR1	ENST00000306739.9	TSL:1 MANE Select	c.454C>G	p.Arg152Gly	missense	Exon 6 of 16	ENSP00000302176.4	Q9BZE9-1
	ASPSCR1	ENST00000584454.5	TSL:1	n.223C>G		non_coding_transcript_exon	Exon 6 of 17	ENSP00000463992.1	J3QR12
	ASPSCR1	ENST00000306729.11	TSL:2	c.454C>G	p.Arg152Gly	missense	Exon 6 of 17	ENSP00000306625.7	Q9BZE9-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152124 Hom.: 0 Cov.: 33

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: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000131 AC: 31 AN: 237502 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.0000631 AC: 92 AN: 1457900 Hom.: 2 Cov.: 32 AF XY: 0.0000869 AC XY: 63 AN XY: 724982

African (AFR) AF: 0.0000299 AC: 1 AN: 33448

American (AMR) AF: 0.000113 AC: 5 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.000760 AC: 65 AN: 85582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51808

Middle Eastern (MID) AF: 0.00123 AC: 7 AN: 5694

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111142

Other (OTH) AF: 0.0000996 AC: 6 AN: 60234

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152124 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74294

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000992 AC: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.083
Sift	Benign	0.069	T
Sift4G	Uncertain	0.025	D
Polyphen		0.76	P
Vest4		0.29
MutPred		0.48		Loss of methylation at R152 (P = 0.0275)
MVP		0.23
MPC		0.14
ClinPred		0.12	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.28
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs368561373; hg19: chr17-79953889;