CD151 p.Ser158Arg

Variant names:

• chr11-837475-A-C
• NM_004357.5:c.472A>C
• CD151 p.Ser158Arg

Your query was ambiguous. Multiple possible variants found:

• chr11-837475-A-C
• chr11-837477-C-A
• chr11-837477-C-G
• chr11-837475-AGC-CGT
• chr11-837475-AGC-CGA
• chr11-837475-AGC-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004357.5(CD151):​c.472A>C​(p.Ser158Arg) variant causes a missense change. 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. Synonymous variant affecting the same amino acid position (i.e. S158S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CD151 NM_004357.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004357.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD151	NM_004357.5	MANE Select	c.472A>C	p.Ser158Arg	missense	Exon 7 of 9	NP_004348.2
	CD151	NM_001039490.2		c.472A>C	p.Ser158Arg	missense	Exon 6 of 8	NP_001034579.1	P48509
	CD151	NM_139029.2		c.472A>C	p.Ser158Arg	missense	Exon 7 of 9	NP_620598.1	P48509

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD151	ENST00000397420.9	TSL:1 MANE Select	c.472A>C	p.Ser158Arg	missense	Exon 7 of 9	ENSP00000380565.3	P48509
	CD151	ENST00000322008.9	TSL:1	c.472A>C	p.Ser158Arg	missense	Exon 7 of 9	ENSP00000324101.4	P48509
	CD151	ENST00000397421.5	TSL:1	c.472A>C	p.Ser158Arg	missense	Exon 6 of 8	ENSP00000380566.1	P48509

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.39	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.95
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-837475;