12-110881144-T-G

Position:

• chr12-110881144-T-G

Variant summary

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

The NM_152591.3(CCDC63):​c.701T>G​(p.Met234Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC63 NM_152591.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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]

ACMG classification

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
CCDC63	NM_152591.3	c.701T>G	p.Met234Arg	missense_variant	7/12	ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000308208.10	c.701T>G	p.Met234Arg	missense_variant	7/12	2	NM_152591.3	ENSP00000312399	P2
CCDC63	ENST00000552694.1	c.464T>G	p.Met155Arg	missense_variant	5/10	1		ENSP00000450217
CCDC63	ENST00000550317.1	n.677T>G		non_coding_transcript_exon_variant	4/4	1
CCDC63	ENST00000545036.5	c.581T>G	p.Met194Arg	missense_variant	6/11	2		ENSP00000445881	A2

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

Jun 24, 2022

The c.701T>G (p.M234R) alteration is located in exon 7 (coding exon 6) of the CCDC63 gene. This alteration results from a T to G substitution at nucleotide position 701, causing the methionine (M) at amino acid position 234 to be replaced by an arginine (R). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.96	.;D;.
Vest4		0.86
MutPred		0.49		.;Loss of ubiquitination at K235 (P = 0.0371);.;
MVP		0.095
MPC		0.32
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.86
gMVP		0.70

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: chr12-111318948;