12-55726197-C-A

Variant names:

• chr12-55726197-C-A
• rs777023084
• NM_001780.6:c.491G>T

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.491G>T​(p.Arg164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD63 NM_001780.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14676878).

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.491G>T	p.Arg164Leu	missense	Exon 6 of 8	NP_001771.1	P08962-1
	CD63	NM_001257389.2		c.491G>T	p.Arg164Leu	missense	Exon 6 of 8	NP_001244318.1	P08962-1
	CD63	NM_001257390.2		c.491G>T	p.Arg164Leu	missense	Exon 6 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.491G>T	p.Arg164Leu	missense	Exon 6 of 8	ENSP00000257857.4	P08962-1
	CD63	ENST00000552692.5	TSL:1	c.491G>T	p.Arg164Leu	missense	Exon 5 of 7	ENSP00000449337.1	P08962-1
	CD63	ENST00000552754.5	TSL:1	c.422G>T	p.Arg141Leu	missense	Exon 5 of 7	ENSP00000446807.1	P08962-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.12
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.0040	B
Vest4		0.38
MutPred		0.49		Gain of catalytic residue at D167 (P = 2e-04)
MVP		0.76
MPC		0.53
ClinPred		0.12	T
GERP RS		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.74
Mutation Taster		=91/9	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: rs777023084; hg19: chr12-56119981;