Variant chr3-48432613-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256964.2(CCDC51):c.1031C>G(p.Ala344Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC51
NM_001256964.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08303869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC51	NM_001256964.2 linkuse as main transcript	c.1031C>G	p.Ala344Gly	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.1031C>G	p.Ala344Gly	missense_variant	4/4	2	NM_001256964.2	ENSP00000379047.2	Q96ER9-1
CCDC51	ENST00000412398.6 linkuse as main transcript	c.704C>G	p.Ala235Gly	missense_variant	4/4	2		ENSP00000401194.2	Q96ER9-2
CCDC51	ENST00000442740.1 linkuse as main transcript	c.704C>G	p.Ala235Gly	missense_variant	4/4	3		ENSP00000392898.1	Q96ER9-2
CCDC51	ENST00000447018.5 linkuse as main transcript	c.704C>G	p.Ala235Gly	missense_variant	4/4	2		ENSP00000412300.1	Q96ER9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249504

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

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

May 24, 2024

The c.1031C>G (p.A344G) alteration is located in exon 4 (coding exon 3) of the CCDC51 gene. This alteration results from a C to G substitution at nucleotide position 1031, causing the alanine (A) at amino acid position 344 to be replaced by a glycine (G). 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

0.099

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.078

.;T;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.71

.;T;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.083

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.15

.;B;.;.

Vest4

0.088

MutPred

0.29

.;Loss of helix (P = 0.0626);.;.;

MVP

0.47

MPC

0.23

ClinPred

0.080

GERP RS

4.0

Varity_R

0.040

gMVP

0.13

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