12-110847068-G-C

Position:

• chr12-110847068-G-C

Variant summary

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

The NM_152591.3(CCDC63):​c.-134G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,072 control chromosomes in the GnomAD database, including 40,553 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 0.73 (40549 hom., cov: 31)
  • Exomes 𝑓: 0.79 (4 hom.)
• Consequence: CCDC63 NM_152591.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC63	NM_152591.3	c.-134G>C		5_prime_UTR_variant	1/12	ENST00000308208.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC63	ENST00000308208.10	c.-134G>C		5_prime_UTR_variant	1/12	2	NM_152591.3	P2
CCDC63	ENST00000552694.1	c.-96G>C		5_prime_UTR_variant	1/10	1
CCDC63	ENST00000550317.1	n.300G>C		non_coding_transcript_exon_variant	1/4	1
CCDC63	ENST00000545036.5	c.-149G>C		5_prime_UTR_variant	1/11	2		A2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110681 AN: 151940 Hom.: 40506 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.786 AC: 11 AN: 14 Hom.: 4 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.833

GnomAD4 genome AF: 0.729 AC: 110786 AN: 152058 Hom.: 40549 Cov.: 31 AF XY: 0.732 AC XY: 54421 AN XY: 74334

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.732

Alfa AF: 0.666 Hom.: 2205

Bravo AF: 0.726

Asia WGS AF: 0.710 AC: 2466 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.67

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: rs2339635; hg19: chr12-111284872;