rs771931556

Variant names:

• chr11-837477-C-G
• rs771931556
• NM_004357.5:c.474C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-837477-C-G
• chr11-837477-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004357.5(CD151):​c.474C>G​(p.Ser158Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CD151 NM_004357.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

Genes affected

CD151 (HGNC:1630): (CD151 molecule (Raph blood group)) 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 and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD151	NM_004357.5	c.474C>G	p.Ser158Arg	missense_variant	Exon 7 of 9	ENST00000397420.9	NP_004348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD151	ENST00000397420.9	c.474C>G	p.Ser158Arg	missense_variant	Exon 7 of 9	1	NM_004357.5	ENSP00000380565.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;.;T;T;.;T;.;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	.;D;D;.;D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.6	M;.;M;M;.;.;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0070	D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.39	T;T;T;T;T;T;T;T;T
Polyphen		0.99	D;.;D;D;.;.;.;.;.
Vest4		0.61
MutPred		0.69		Gain of methylation at S158 (P = 0.0399);Gain of methylation at S158 (P = 0.0399);Gain of methylation at S158 (P = 0.0399);Gain of methylation at S158 (P = 0.0399);.;Gain of methylation at S158 (P = 0.0399);Gain of methylation at S158 (P = 0.0399);Gain of methylation at S158 (P = 0.0399);Gain of methylation at S158 (P = 0.0399);
MVP		0.90
MPC		0.63
ClinPred		0.98	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.54		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.54		Position offset: 0

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

Publications

LitVar

Other links and lift over

dbSNP: rs771931556; hg19: chr11-837477;