rs10774610

Positions:

• chr12-110902439-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152591.3(CCDC63):​c.1343-2149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,956 control chromosomes in the GnomAD database, including 9,672 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 0.35 (9672 hom., cov: 31)
• Consequence: CCDC63 NM_152591.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC63	NM_152591.3	c.1343-2149T>C		intron_variant		ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000308208.10	c.1343-2149T>C		intron_variant		2	NM_152591.3	ENSP00000312399.5
CCDC63	ENST00000552694.1	c.1106-2149T>C		intron_variant		1		ENSP00000450217.1
CCDC63	ENST00000545036.5	c.1223-2149T>C		intron_variant		2		ENSP00000445881.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53368 AN: 151832 Hom.: 9666 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.351 AC: 53411 AN: 151956 Hom.: 9672 Cov.: 31 AF XY: 0.352 AC XY: 26165 AN XY: 74276

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.301

Alfa AF: 0.322 Hom.: 17319

Bravo AF: 0.353

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.28
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs10774610; hg19: chr12-111340243;