chr4-98486749-G-T

Variant names:

• chr4-98486749-G-T
• rs193921080
• NM_005723.4:c.268C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005723.4(TSPAN5):​c.268C>A​(p.Leu90Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPAN5 NM_005723.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.94

Genes affected

TSPAN5 (HGNC:17753): (tetraspanin 5) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPAN5	NM_005723.4	c.268C>A	p.Leu90Ile	missense_variant	Exon 3 of 8	ENST00000305798.8	NP_005714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPAN5	ENST00000305798.8	c.268C>A	p.Leu90Ile	missense_variant	Exon 3 of 8	1	NM_005723.4	ENSP00000307701.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

-

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T;.;.;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	2.9	M;.;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;.;D
Polyphen		1.0	D;.;.;.
Vest4		0.72
MutPred		0.81		Gain of methylation at K92 (P = 0.045);.;.;.;
MVP		0.80
MPC		1.9
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.36
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs193921080; hg19: chr4-99407900; COSMIC: COSV59873743; COSMIC: COSV59873743;