NM_004357.5:c.477C>A

Variant names:

• chr11-837480-C-A
• rs1162525540
• NM_004357.5:c.477C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_004357.5(CD151):​c.477C>A​(p.Asn159Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.07

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 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity CD151_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD151	NM_004357.5	c.477C>A	p.Asn159Lys	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.477C>A	p.Asn159Lys	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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.;T;T;.;T;.;T;T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.0029
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	.;D;D;.;D;D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	2.0	M;.;M;M;.;.;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D;D;D;D;N;N;D;D;N
REVEL	Uncertain	0.35
Sift	Benign	0.22	T;D;T;T;T;D;D;T;D
Sift4G	Benign	0.77	T;T;T;T;T;T;T;T;T
Polyphen		0.20	B;.;B;B;.;.;.;.;.
Vest4		0.65
MutPred		0.55		Gain of catalytic residue at N159 (P = 0.003);Gain of catalytic residue at N159 (P = 0.003);Gain of catalytic residue at N159 (P = 0.003);Gain of catalytic residue at N159 (P = 0.003);.;Gain of catalytic residue at N159 (P = 0.003);Gain of catalytic residue at N159 (P = 0.003);Gain of catalytic residue at N159 (P = 0.003);Gain of catalytic residue at N159 (P = 0.003);
MVP		0.78
MPC		0.21
ClinPred		0.87	D
GERP RS		3.5
Varity_R		0.51
gMVP		0.84

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: rs1162525540; hg19: chr11-837480;