rs12303008

Variant names:

• chr12-110847027-C-G
• rs12303008
• ENST00000550317.1:n.259C>G

Variant summary

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

The ENST00000550317.1(CCDC63):​n.259C>G 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 0.0968 in 152,228 control chromosomes in the GnomAD database, including 1,125 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 0.097 (1125 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC63 ENST00000550317.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683
• Publications: 1 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC63	NM_152591.3	c.-175C>G		5_prime_UTR_variant	Exon 1 of 12	ENST00000308208.10	NP_689804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC63	ENST00000550317.1	n.259C>G		non_coding_transcript_exon_variant	Exon 1 of 4	1
CCDC63	ENST00000308208.10	c.-175C>G		5_prime_UTR_variant	Exon 1 of 12	2	NM_152591.3	ENSP00000312399.5
CCDC63	ENST00000552694.1	c.-137C>G		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000450217.1
CCDC63	ENST00000545036.5	c.-190C>G		5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000445881.1

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14709 AN: 152110 Hom.: 1122 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0988

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0968 AC: 14733 AN: 152228 Hom.: 1125 Cov.: 32 AF XY: 0.0953 AC XY: 7094 AN XY: 74432

African (AFR) AF: 0.213 AC: 8844 AN: 41528

American (AMR) AF: 0.0628 AC: 961 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3472

East Asian (EAS) AF: 0.00832 AC: 43 AN: 5170

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4826

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0509 AC: 3465 AN: 68012

Other (OTH) AF: 0.0973 AC: 205 AN: 2106

Alfa AF: 0.0716 Hom.: 87

Bravo AF: 0.104

Asia WGS AF: 0.0570 AC: 201 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.47
PhyloP100		0.68
PromoterAI		0.078	Neutral
Mutation Taster		=299/1	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: rs12303008; hg19: chr12-111284831;