3-48432591-T-A

Position:

• chr3-48432591-T-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.1053A>T​(p.Glu351Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC51 NM_001256964.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0110

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=0.07497722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC51	NM_001256964.2	c.1053A>T	p.Glu351Asp	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.1053A>T	p.Glu351Asp	missense_variant	4/4	2	NM_001256964.2	ENSP00000379047.2
CCDC51	ENST00000412398.6	c.726A>T	p.Glu242Asp	missense_variant	4/4	2		ENSP00000401194.2
CCDC51	ENST00000442740.1	c.726A>T	p.Glu242Asp	missense_variant	4/4	3		ENSP00000392898.1
CCDC51	ENST00000447018.5	c.726A>T	p.Glu242Asp	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

Nov 15, 2024

The c.1053A>T (p.E351D) alteration is located in exon 4 (coding exon 3) of the CCDC51 gene. This alteration results from a A to T substitution at nucleotide position 1053, causing the glutamic acid (E) at amino acid position 351 to be replaced by an aspartic acid (D). 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	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.8
DANN	Benign	0.96
DEOGEN2	Benign	0.016	.;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.69	.;T;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;M;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.81	N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.029	.;B;.;.
Vest4		0.035
MutPred		0.17		.;Loss of sheet (P = 0.1907);.;.;
MVP		0.40
MPC		0.21
ClinPred		0.14	T
GERP RS		3.0
Varity_R		0.039
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-48474001;