Variant chr3-48432973-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256964.2(CCDC51):c.671G>A(p.Arg224His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,208 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 1 hom. )

Consequence

CCDC51
NM_001256964.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC51	NM_001256964.2 linkuse as main transcript	c.671G>A	p.Arg224His	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.671G>A	p.Arg224His	missense_variant	4/4	2	NM_001256964.2	ENSP00000379047.2	Q96ER9-1
CCDC51	ENST00000412398.6 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	4/4	2		ENSP00000401194.2	Q96ER9-2
CCDC51	ENST00000442740.1 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	4/4	3		ENSP00000392898.1	Q96ER9-2
CCDC51	ENST00000447018.5 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	4/4	2		ENSP00000412300.1	Q96ER9-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000116

AC:

AN:

249444

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135372

show subpopulations

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 SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000939

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000227

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.671G>A (p.R224H) alteration is located in exon 4 (coding exon 3) of the CCDC51 gene. This alteration results from a G to A substitution at nucleotide position 671, causing the arginine (R) at amino acid position 224 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.045

.;T;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

.;D;.;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.9

.;L;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

1.0

.;D;.;.

Vest4

0.83

MutPred

0.54

.;Loss of MoRF binding (P = 0.0137);.;.;

MVP

0.83

MPC

0.69

ClinPred

0.35

GERP RS

4.9

Varity_R

0.23

gMVP

0.46

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