12-110853485-G-C

Position:

• chr12-110853485-G-C

Variant summary

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

The NM_152591.3(CCDC63):​c.90G>C​(p.Glu30Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC63 NM_152591.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.985

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	UniProt
CCDC63	NM_152591.3	c.90G>C	p.Glu30Asp	missense_variant	3/12	ENST00000308208.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC63	ENST00000308208.10	c.90G>C	p.Glu30Asp	missense_variant	3/12	2	NM_152591.3	P2
CCDC63	ENST00000552694.1	c.-58-5101G>C		intron_variant		1
CCDC63	ENST00000550317.1	n.338-5101G>C		intron_variant, non_coding_transcript_variant		1
CCDC63	ENST00000545036.5	c.-31G>C		5_prime_UTR_variant	2/11	2		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 09, 2023

The c.90G>C (p.E30D) alteration is located in exon 3 (coding exon 2) of the CCDC63 gene. This alteration results from a G to C substitution at nucleotide position 90, causing the glutamic acid (E) at amino acid position 30 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	0.23
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.39		Loss of methylation at K33 (P = 0.0824);
MVP		0.63
MPC		0.33
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.69
gMVP		0.38

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: chr12-111291289;