NM_004616.3:c.160G>T

Variant names:

• chr12-71139812-C-A
• NM_004616.3:c.160G>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.160G>T​(p.Val54Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. V54I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPAN8 NM_004616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12

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=0.2440696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.160G>T	p.Val54Phe	missense_variant	Exon 4 of 9	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.160G>T	p.Val54Phe	missense_variant	Exon 3 of 8		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.160G>T	p.Val54Phe	missense_variant	Exon 4 of 9	1	NM_004616.3	ENSP00000247829.3
TSPAN8	ENST00000393330.6	c.160G>T	p.Val54Phe	missense_variant	Exon 7 of 12	1		ENSP00000377003.2
TSPAN8	ENST00000546561.2	c.160G>T	p.Val54Phe	missense_variant	Exon 3 of 8	1		ENSP00000447160.1
TSPAN8	ENST00000552786.1	n.*21G>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.38	.;.;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.44
Sift	Benign	0.046	D;D;D
Sift4G	Uncertain	0.045	D;D;D
Polyphen		0.86	P;P;P
Vest4		0.099
MutPred		0.52		Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP		0.66
MPC		0.39
ClinPred		0.64	D
GERP RS		-1.9
Varity_R		0.15
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-71533592;