11-837514-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004357.5(CD151):c.511C>T(p.Arg171Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,612,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R171H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

CD151
NM_004357.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.24

Variant links:

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]

CD151 links:

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]

POLR2L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3483618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD151	NM_004357.5 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	7/9	ENST00000397420.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD151	ENST00000397420.9 linkuse as main transcript	c.511C>T	p.Arg171Cys	missense_variant	7/9	1	NM_004357.5	P3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000880

AC:

AN:

249940

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1460704

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Dec 14, 2023

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 171 of the CD151 protein (p.Arg171Cys). This variant is present in population databases (rs139042921, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CD151-related conditions. ClinVar contains an entry for this variant (Variation ID: 1028737). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Epidermolysis bullosa simplex 7, with nephropathy and deafness

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Jul 23, 2019

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.;D;D;.;T;.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.97

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.35

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.1

M;.;M;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.020

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.044

D;T;D;D;D;T;T;D

Polyphen

0.96

D;.;D;D;.;.;.;.

Vest4

0.53

MVP

0.87

MPC

0.42

ClinPred

0.27

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over