rs994190722

Variant names:

• chr12-55726769-G-T
• rs994190722
• NM_001780.6:c.357C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-55726769-G-T
• chr12-55726769-G-A
• chr12-55726769-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001780.6(CD63):​c.357C>A​(p.Phe119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,461,792 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. F119Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: CD63 NM_001780.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20025098).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251482 AF XY: 0.0000147

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: 0.0000287 AC: 42 AN: 1461792 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727202

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: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111922

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000282 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Benign	0.77
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.80	N
PhyloP100		2.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.46	N
REVEL	Uncertain	0.37
Sift	Benign	0.67	T
Sift4G	Benign	1.0	T
Polyphen		0.015	B
Vest4		0.14
MutPred		0.59		Gain of catalytic residue at E114 (P = 0.1781)
MVP		0.82
MPC		0.52
ClinPred		0.051	T
GERP RS		4.3
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.13
gMVP		0.77
Mutation Taster		=67/33	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: rs994190722; hg19: chr12-56120553;