chr3-48432711-C-A

Position:

• chr3-48432711-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256964.2(CCDC51):​c.933G>T​(p.Arg311Ser) 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. 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)
• Consequence: CCDC51 NM_001256964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.255

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]

ACMG classification

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=0.10511476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC51	NM_001256964.2	c.933G>T	p.Arg311Ser	missense_variant	4/4	ENST00000395694.7	NP_001243893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC51	ENST00000395694.7	c.933G>T	p.Arg311Ser	missense_variant	4/4	2	NM_001256964.2	ENSP00000379047.2
CCDC51	ENST00000412398.6	c.606G>T	p.Arg202Ser	missense_variant	4/4	2		ENSP00000401194.2
CCDC51	ENST00000442740.1	c.606G>T	p.Arg202Ser	missense_variant	4/4	3		ENSP00000392898.1
CCDC51	ENST00000447018.5	c.606G>T	p.Arg202Ser	missense_variant	4/4	2		ENSP00000412300.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.933G>T (p.R311S) alteration is located in exon 4 (coding exon 3) of the CCDC51 gene. This alteration results from a G to T substitution at nucleotide position 933, causing the arginine (R) at amino acid position 311 to be replaced by a serine (S). 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	0.20
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0089	.;T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	.;T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.20	N;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.040	D;D;D;D
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.47	.;P;.;.
Vest4		0.15
MutPred		0.14		.;Gain of relative solvent accessibility (P = 0.0166);.;.;
MVP		0.62
MPC		0.29
ClinPred		0.14	T
GERP RS		2.0
Varity_R		0.23
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-48474121;