12-110895818-T-C

Variant names:

• chr12-110895818-T-C
• rs10849915
• NM_152591.3:c.1149+2668T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152591.3(CCDC63):​c.1149+2668T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,106 control chromosomes in the GnomAD database, including 11,976 homozygotes. 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: 𝑓 0.38 (11976 hom., cov: 32)
• Consequence: CCDC63 NM_152591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC63	NM_152591.3	c.1149+2668T>C		intron_variant	Intron 9 of 11	ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000308208.10	c.1149+2668T>C		intron_variant	Intron 9 of 11	2	NM_152591.3	ENSP00000312399.5
CCDC63	ENST00000552694.1	c.912+2668T>C		intron_variant	Intron 7 of 9	1		ENSP00000450217.1
CCDC63	ENST00000545036.5	c.1029+2668T>C		intron_variant	Intron 8 of 10	2		ENSP00000445881.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58348 AN: 151988 Hom.: 11958 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58409 AN: 152106 Hom.: 11976 Cov.: 32 AF XY: 0.383 AC XY: 28470 AN XY: 74364

African (AFR) AF: 0.523 AC: 21703 AN: 41470

American (AMR) AF: 0.372 AC: 5684 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5184

South Asian (SAS) AF: 0.282 AC: 1359 AN: 4820

European-Finnish (FIN) AF: 0.388 AC: 4099 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22710 AN: 67990

Other (OTH) AF: 0.325 AC: 685 AN: 2108

Alfa AF: 0.338 Hom.: 31208

Bravo AF: 0.390

Asia WGS AF: 0.214 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.49
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10849915; hg19: chr12-111333622; COSMIC: COSV57530831;