Genetic Variant CD63:p.Phe119Leu (chr12-55726769-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001780.6(CD63):c.357C>G(p.Phe119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F119Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CD63
NM_001780.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.58

Publications

0 publications found

Variant links:

Genes affected

CD63 (HGNC:1692): (CD63 molecule) 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. The encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with Hermansky-Pudlak syndrome. Also this gene has been associated with tumor progression. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Apr 2012]

CD63 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21100521).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001780.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD63	NM_001780.6	MANE Select	c.357C>G	p.Phe119Leu	missense	Exon 5 of 8	NP_001771.1	P08962-1
CD63	NM_001257389.2		c.357C>G	p.Phe119Leu	missense	Exon 5 of 8	NP_001244318.1	P08962-1
CD63	NM_001257390.2		c.357C>G	p.Phe119Leu	missense	Exon 5 of 8	NP_001244319.1	P08962-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD63	ENST00000257857.9	TSL:1 MANE Select	c.357C>G	p.Phe119Leu	missense	Exon 5 of 8	ENSP00000257857.4	P08962-1
CD63	ENST00000552692.5	TSL:1	c.357C>G	p.Phe119Leu	missense	Exon 4 of 7	ENSP00000449337.1	P08962-1
CD63	ENST00000552754.5	TSL:1	c.288C>G	p.Phe96Leu	missense	Exon 4 of 7	ENSP00000446807.1	P08962-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111922

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.14

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.74

M_CAP

Benign

0.069

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.80

PhyloP100

2.6

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.46

REVEL

Uncertain

0.37

Sift

Benign

0.67

Sift4G

Benign

1.0

Polyphen

0.015

Vest4

0.14

MutPred

0.59

Gain of catalytic residue at E114 (P = 0.1781)

MVP

0.82

MPC

0.52

ClinPred

0.28

GERP RS

4.3

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.13

gMVP

0.77

Mutation Taster

=67/33

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over