chr12-57745197-G-A

Variant names:

• chr12-57745197-G-A
• rs753456818
• NM_005981.5:c.43G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005981.5(TSPAN31):​c.43G>A​(p.Ala15Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TSPAN31 NM_005981.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71

Genes affected

TSPAN31 (HGNC:10539): (tetraspanin 31) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3858596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN31	NM_005981.5	c.43G>A	p.Ala15Thr	missense_variant	Exon 1 of 6	ENST00000257910.8	NP_005972.1
TSPAN31	NM_001330168.2	c.43G>A	p.Ala15Thr	missense_variant	Exon 1 of 4		NP_001317097.1
TSPAN31	NM_001330169.2	c.-206G>A		5_prime_UTR_variant	Exon 1 of 6		NP_001317098.1
TSPAN31	XM_024449123.2	c.-414G>A		upstream_gene_variant			XP_024304891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN31	ENST00000257910.8	c.43G>A	p.Ala15Thr	missense_variant	Exon 1 of 6	1	NM_005981.5	ENSP00000257910.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.11	T;D;D
Sift4G	Benign	0.13	T;T;D
Polyphen		0.94	P;P;.
Vest4		0.44
MutPred		0.54		Loss of ubiquitination at K10 (P = 0.1037);Loss of ubiquitination at K10 (P = 0.1037);Loss of ubiquitination at K10 (P = 0.1037);
MVP		0.82
MPC		0.91
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.53
gMVP		0.40

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: rs753456818; hg19: chr12-58138980;