12-110847068-G-C

Variant names:

• chr12-110847068-G-C
• rs2339635
• ENST00000550317.1:n.300G>C

Variant summary

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

The ENST00000550317.1(CCDC63):​n.300G>C variant causes a non coding transcript exon 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 ENST00000550317.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550317.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC63	NM_152591.3	MANE Select	c.-134G>C		5_prime_UTR	Exon 1 of 12	NP_689804.1
	CCDC63	NM_001286243.2		c.-149G>C		5_prime_UTR	Exon 1 of 11	NP_001273172.1
	CCDC63	NM_001286244.2		c.-96G>C		5_prime_UTR	Exon 1 of 10	NP_001273173.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC63	ENST00000550317.1	TSL:1	n.300G>C		non_coding_transcript_exon	Exon 1 of 4
	CCDC63	ENST00000308208.10	TSL:2 MANE Select	c.-134G>C		5_prime_UTR	Exon 1 of 12	ENSP00000312399.5
	CCDC63	ENST00000552694.1	TSL:1	c.-96G>C		5_prime_UTR	Exon 1 of 10	ENSP00000450217.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 10 AN: 12

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.764 AC: 31701 AN: 41504

American (AMR) AF: 0.755 AC: 11549 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2123 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3348 AN: 5148

South Asian (SAS) AF: 0.758 AC: 3660 AN: 4826

European-Finnish (FIN) AF: 0.768 AC: 8117 AN: 10568

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47840 AN: 67922

Other (OTH) AF: 0.732 AC: 1545 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		-1.5
PromoterAI		0.0017	Neutral
Mutation Taster		=300/0	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: rs2339635; hg19: chr12-111284872;