12-110858645-T-C

Position:

• chr12-110858645-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001286244.2(CCDC63):​c.2T>C​(p.Met1?) variant causes a start lost 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC63 NM_001286244.2 start_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

Genes affected

CCDC63 (HGNC:26669): (coiled-coil domain containing 63) Predicted to be involved in cilium movement; outer dynein arm assembly; and spermatid development. Predicted to be active in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CCDC63 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC63	NM_152591.3	c.239T>C	p.Met80Thr	missense_variant	4/12	ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000552694.1	c.2T>C	p.Met1?	start_lost	2/10	1		ENSP00000450217.1
CCDC63	ENST00000308208.10	c.239T>C	p.Met80Thr	missense_variant	4/12	2	NM_152591.3	ENSP00000312399.5
CCDC63	ENST00000550317.1	n.397T>C		non_coding_transcript_exon_variant	2/4	1
CCDC63	ENST00000545036.5	c.119T>C	p.Met40Thr	missense_variant	3/11	2		ENSP00000445881.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Sep 10, 2024

The c.239T>C (p.M80T) alteration is located in exon 4 (coding exon 3) of the CCDC63 gene. This alteration results from a T to C substitution at nucleotide position 239, causing the methionine (M) at amino acid position 80 to be replaced by a threonine (T). 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	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.0043	.;T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.40	T;T;D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	.;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.76	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.22	T;T;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.0030	.;B;.
Vest4		0.23
MutPred		0.41		.;Loss of stability (P = 0.0068);.;
MVP		0.014
MPC		0.057
ClinPred		0.027	T
GERP RS		3.3
Varity_R		0.064
gMVP		0.088

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: chr12-111296449;