NM_024083.4:c.116C>T

Variant names:

• chr17-81979197-C-T
• rs2041715603
• NM_024083.4:c.116C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024083.4(ASPSCR1):​c.116C>T​(p.Thr39Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASPSCR1 NM_024083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34660518).

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.116C>T	p.Thr39Met	missense	Exon 2 of 16	NP_076988.1	Q9BZE9-1
	ASPSCR1	NM_001251888.2		c.116C>T	p.Thr39Met	missense	Exon 2 of 17	NP_001238817.1	Q9BZE9-2
	ASPSCR1	NM_001330528.2		c.-74+1449C>T		intron	N/A	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.116C>T	p.Thr39Met	missense	Exon 2 of 16	ENSP00000302176.4	Q9BZE9-1
	ASPSCR1	ENST00000584454.5	TSL:1	n.-116C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 17	ENSP00000463992.1	J3QR12
	ASPSCR1	ENST00000584454.5	TSL:1	n.-116C>T		non_coding_transcript_exon	Exon 2 of 17	ENSP00000463992.1	J3QR12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.46		Gain of catalytic residue at V35 (P = 0.0245)
MVP		0.52
MPC		0.11
ClinPred		0.85	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.067
gMVP		0.44
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs2041715603; hg19: chr17-79937073; COSMIC: COSV100144880;