rs751851666

Variant names:

• chr12-57746249-G-C
• rs751851666
• NM_005981.5:c.305G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005981.5(TSPAN31):​c.305G>C​(p.Ser102Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: TSPAN31 NM_005981.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.539
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11853996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005981.5. 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
	TSPAN31	NM_005981.5	MANE Select	c.305G>C	p.Ser102Thr	missense	Exon 3 of 6	NP_005972.1	Q12999
	TSPAN31	NM_001330169.2		c.71G>C	p.Ser24Thr	missense	Exon 3 of 6	NP_001317098.1	B4DFJ7
	TSPAN31	NM_001330168.2		c.64-340G>C		intron	N/A	NP_001317097.1	F8VWE0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN31	ENST00000257910.8	TSL:1 MANE Select	c.305G>C	p.Ser102Thr	missense	Exon 3 of 6	ENSP00000257910.3	Q12999
	TSPAN31	ENST00000547992.5	TSL:1	c.192+376G>C		intron	N/A	ENSP00000448209.1	F8VS78
	TSPAN31	ENST00000870605.1		c.305G>C	p.Ser102Thr	missense	Exon 3 of 6	ENSP00000540664.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251468 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461546 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000201 AC: 9 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111708

Other (OTH) AF: 0.0000828 AC: 5 AN: 60382

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

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	0.088
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.66	N
PhyloP100		0.54
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.083
Sift	Benign	0.35	T
Sift4G	Benign	0.26	T
Polyphen		0.071	B
Vest4		0.32
MutPred		0.34		Loss of glycosylation at S102 (P = 0.0703)
MVP		0.69
MPC		0.32
ClinPred		0.039	T
GERP RS		0.95
Varity_R		0.059
gMVP		0.52
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs751851666; hg19: chr12-58140032;