Variant 12-55726739-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001780.6(CD63):c.387C>T(p.Asn129Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,614,036 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 127 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 135 hom. )

Consequence

CD63
NM_001780.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.168

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-55726739-G-A is Benign according to our data. Variant chr12-55726739-G-A is described in ClinVar as [Benign]. Clinvar id is 776898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.168 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD63	NM_001780.6 linkuse as main transcript	c.387C>T	p.Asn129Asn	synonymous_variant	5/8	ENST00000257857.9	NP_001771.1	P08962-1A0A024RB05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD63	ENST00000257857.9 linkuse as main transcript	c.387C>T	p.Asn129Asn	synonymous_variant	5/8	1	NM_001780.6	ENSP00000257857.4	P08962-1
CD63	ENST00000552067.5 linkuse as main transcript	c.108C>T	p.Asn36Asn	synonymous_variant	3/6	5		ENSP00000449684.1	F8VV56
CD63	ENST00000550050.5 linkuse as main transcript	n.*53C>T		non_coding_transcript_exon_variant	5/8	5		ENSP00000449435.1	F8VX62
CD63	ENST00000550050.5 linkuse as main transcript	n.*53C>T		3_prime_UTR_variant	5/8	5		ENSP00000449435.1	F8VX62

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3287

AN:

152072

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00539

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00878

AC:

2207

AN:

251494

Hom.:

AF XY:

0.00644

AC XY:

875

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0745

Gnomad AMR exome

AF:

0.0246

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00381

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00570

GnomAD4 exome

AF:

0.00289

AC:

4229

AN:

1461846

Hom.:

135

Cov.:

AF XY:

0.00257

AC XY:

1868

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0774

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00174

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.00606

GnomAD4 genome

AF:

0.0218

AC:

3321

AN:

152190

Hom.:

127

Cov.:

AF XY:

0.0214

AC XY:

1591

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0723

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00540

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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