chr12-110898985-G-C

Position:

• chr12-110898985-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152591.3(CCDC63):​c.1202G>C​(p.Gly401Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC63 NM_152591.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0680

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039664567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC63	NM_152591.3	c.1202G>C	p.Gly401Ala	missense_variant	10/12	ENST00000308208.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC63	ENST00000308208.10	c.1202G>C	p.Gly401Ala	missense_variant	10/12	2	NM_152591.3	P2
CCDC63	ENST00000552694.1	c.965G>C	p.Gly322Ala	missense_variant	8/10	1
CCDC63	ENST00000545036.5	c.1082G>C	p.Gly361Ala	missense_variant	9/11	2		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460952 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Nov 14, 2023

The c.1202G>C (p.G401A) alteration is located in exon 10 (coding exon 9) of the CCDC63 gene. This alteration results from a G to C substitution at nucleotide position 1202, causing the glycine (G) at amino acid position 401 to be replaced by an alanine (A). 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	0.080
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.78
DANN	Benign	0.85
DEOGEN2	Benign	0.0050	.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.21	T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.040	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.53	N;N;N
REVEL	Benign	0.019
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		0.065	.;B;.
Vest4		0.19
MutPred		0.23		.;Loss of ubiquitination at K405 (P = 0.092);.;
MVP		0.030
MPC		0.058
ClinPred		0.094	T
GERP RS		-4.5
Varity_R		0.041
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-111336789;