chr12-71132782-T-A

Variant names:

• chr12-71132782-T-A
• rs1048832652
• NM_004616.3:c.487A>T

Variant summary

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

The NM_004616.3(TSPAN8):​c.487A>T​(p.Asn163Tyr) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPAN8 NM_004616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3934936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN8	NM_004616.3	c.487A>T	p.Asn163Tyr	missense_variant	Exon 7 of 9	ENST00000247829.8	NP_004607.1
TSPAN8	NM_001369760.1	c.487A>T	p.Asn163Tyr	missense_variant	Exon 6 of 8		NP_001356689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN8	ENST00000247829.8	c.487A>T	p.Asn163Tyr	missense_variant	Exon 7 of 9	1	NM_004616.3	ENSP00000247829.3
TSPAN8	ENST00000393330.6	c.487A>T	p.Asn163Tyr	missense_variant	Exon 10 of 12	1		ENSP00000377003.2
TSPAN8	ENST00000546561.2	c.487A>T	p.Asn163Tyr	missense_variant	Exon 6 of 8	1		ENSP00000447160.1
TSPAN8	ENST00000552128.2	n.351A>T		non_coding_transcript_exon_variant	Exon 4 of 6	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	0.046
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.61	.;.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.019	D;D;D
Sift4G	Uncertain	0.029	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.32
MutPred		0.49		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.86
MPC		0.42
ClinPred		0.79	D
GERP RS		2.4
Varity_R		0.20
gMVP		0.61

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: rs1048832652; hg19: chr12-71526562;