chr12-71125345-C-A

Variant names:

• chr12-71125345-C-A
• rs144070931
• NM_004616.3:c.703G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004616.3(TSPAN8):​c.703G>T​(p.Gly235Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,078 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TSPAN8 NM_004616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

Genes affected

TSPAN8 (HGNC:11855): (tetraspanin 8) 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 a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25391585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.703G>T	p.Gly235Trp	missense_variant	Exon 9 of 9	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.703G>T	p.Gly235Trp	missense_variant	Exon 8 of 8		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.703G>T	p.Gly235Trp	missense_variant	Exon 9 of 9	1	NM_004616.3	ENSP00000247829.3
TSPAN8	ENST00000393330.6	c.703G>T	p.Gly235Trp	missense_variant	Exon 12 of 12	1		ENSP00000377003.2
TSPAN8	ENST00000546561.2	c.703G>T	p.Gly235Trp	missense_variant	Exon 8 of 8	1		ENSP00000447160.1
TSPAN8	ENST00000552128.2	n.567G>T		non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460078 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726348

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.62	.;.;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.8	M;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.30
MutPred		0.37		Loss of disorder (P = 0.0014);Loss of disorder (P = 0.0014);Loss of disorder (P = 0.0014);
MVP		0.54
MPC		0.51
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs144070931; hg19: chr12-71519125; COSMIC: COSV105854208;