11-837475-AGC-TCA

Variant names:

• chr11-837475-AGC-TCA
• NM_004357.5:c.472_474delAGCinsTCA
• CD151 p.159

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_004357.5(CD151):​c.472_474delAGCinsTCA​(p.159) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.67
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.472_474delAGCinsTCA	p.159	synonymous	N/A	NP_004348.2
	CD151	NM_001039490.2		c.472_474delAGCinsTCA	p.159	synonymous	N/A	NP_001034579.1	P48509
	CD151	NM_139029.2		c.472_474delAGCinsTCA	p.159	synonymous	N/A	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.472_474delAGCinsTCA	p.159	synonymous	N/A	ENSP00000380565.3	P48509
	CD151	ENST00000322008.9	TSL:1	c.472_474delAGCinsTCA	p.159	synonymous	N/A	ENSP00000324101.4	P48509
	CD151	ENST00000397421.5	TSL:1	c.472_474delAGCinsTCA	p.159	synonymous	N/A	ENSP00000380566.1	P48509

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.7

Splicing

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;