Variant chr3-48432676-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001256964.2(CCDC51):c.968A>G(p.Gln323Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000971 in 1,614,268 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 7 hom. )

Consequence

CCDC51
NM_001256964.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

CCDC51 (HGNC:25714): (coiled-coil domain containing 51) Enables mitochondrial ATP-gated potassium channel activity. Involved in potassium ion transmembrane transport. Is integral component of mitochondrial inner membrane. Part of mitochondrial ATP-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

CCDC51 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005668789).

BP6

Variant 3-48432676-T-C is Benign according to our data. Variant chr3-48432676-T-C is described in ClinVar as [Benign]. Clinvar id is 784001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00532 (810/152382) while in subpopulation AFR AF= 0.0186 (773/41590). AF 95% confidence interval is 0.0175. There are 5 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC51	NM_001256964.2 linkuse as main transcript	c.968A>G	p.Gln323Arg	missense_variant	4/4	ENST00000395694.7	NP_001243893.1	Q96ER9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC51	ENST00000395694.7 linkuse as main transcript	c.968A>G	p.Gln323Arg	missense_variant	4/4	2	NM_001256964.2	ENSP00000379047.2	Q96ER9-1
CCDC51	ENST00000412398.6 linkuse as main transcript	c.641A>G	p.Gln214Arg	missense_variant	4/4	2		ENSP00000401194.2	Q96ER9-2
CCDC51	ENST00000442740.1 linkuse as main transcript	c.641A>G	p.Gln214Arg	missense_variant	4/4	3		ENSP00000392898.1	Q96ER9-2
CCDC51	ENST00000447018.5 linkuse as main transcript	c.641A>G	p.Gln214Arg	missense_variant	4/4	2		ENSP00000412300.1	Q96ER9-2

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

809

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00139

AC:

348

AN:

249532

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000519

AC:

758

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

326

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00532

AC:

810

AN:

152382

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00598

ESP6500AA

AF:

0.0155

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00172

AC:

208

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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	Dec 28, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.1

DANN

Benign

0.84

DEOGEN2

Benign

0.056

.;T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.52

.;T;.;T

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.0010

.;B;.;.

Vest4

0.075

MVP

0.56

MPC

0.25

ClinPred

0.0061

GERP RS

0.87

Varity_R

0.089

gMVP

0.47

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