chr12-110898940-T-A

Position:

• chr12-110898940-T-A

Variant summary

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

The NM_152591.3(CCDC63):​c.1157T>A​(p.Leu386Gln) 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: 4.55

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.1157T>A	p.Leu386Gln	missense_variant	10/12	ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000308208.10	c.1157T>A	p.Leu386Gln	missense_variant	10/12	2	NM_152591.3	ENSP00000312399	P2
CCDC63	ENST00000552694.1	c.920T>A	p.Leu307Gln	missense_variant	8/10	1		ENSP00000450217
CCDC63	ENST00000545036.5	c.1037T>A	p.Leu346Gln	missense_variant	9/11	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

Jan 30, 2024

The c.1157T>A (p.L386Q) alteration is located in exon 10 (coding exon 9) of the CCDC63 gene. This alteration results from a T to A substitution at nucleotide position 1157, causing the leucine (L) at amino acid position 386 to be replaced by a glutamine (Q). 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	0.24
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.1	.;M;.
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0030	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.87
MutPred		0.49		.;Loss of stability (P = 0.0148);.;
MVP		0.13
MPC		0.35
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.77

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: chr12-111336744;