rs761342884

Variant names:

• chr12-55727198-C-T
• rs761342884
• NM_001780.6:c.208G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001257400.2(CD63):​c.-39G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,576 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 (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CD63 NM_001257400.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3473182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257400.2. 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
	CD63	NM_001780.6	MANE Select	c.208G>A	p.Val70Met	missense	Exon 3 of 8	NP_001771.1	P08962-1
	CD63	NM_001257400.2		c.-39G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001244329.1	P08962-3
	CD63	NM_001257401.2		c.-39G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001244330.1	P08962-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD63	ENST00000257857.9	TSL:1 MANE Select	c.208G>A	p.Val70Met	missense	Exon 3 of 8	ENSP00000257857.4	P08962-1
	CD63	ENST00000552692.5	TSL:1	c.208G>A	p.Val70Met	missense	Exon 2 of 7	ENSP00000449337.1	P08962-1
	CD63	ENST00000552754.5	TSL:1	c.139G>A	p.Val47Met	missense	Exon 2 of 7	ENSP00000446807.1	P08962-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251226 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461576 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727076

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.054
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.50	N
REVEL	Uncertain	0.42
Sift	Benign	0.075	T
Sift4G	Benign	0.067	T
Polyphen		0.038	B
Vest4		0.43
MutPred		0.54		Gain of catalytic residue at V70 (P = 0)
MVP		0.79
MPC		0.58
ClinPred		0.40	T
GERP RS		4.5
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.30
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs761342884; hg19: chr12-56120982;