Genetic Variant CCDC63:c.1149+2668T>C (chr12-110895818-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.244

Variant links:

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]

CCDC63 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 link	c.1149+2668T>C		intron_variant	Intron 9 of 11	ENST00000308208.10	NP_689804.1	Q8NA47-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC63	ENST00000308208.10 link	c.1149+2668T>C	intron_variant	Intron 9 of 11	2	NM_152591.3	ENSP00000312399.5	Q8NA47-1
CCDC63	ENST00000552694.1 link	c.912+2668T>C	intron_variant	Intron 7 of 9	1		ENSP00000450217.1	G3V217
CCDC63	ENST00000545036.5 link	c.1029+2668T>C	intron_variant	Intron 8 of 10	2		ENSP00000445881.1	Q8NA47-2

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58348

AN:

151988

Hom.:

11958

Cov.:

show subpopulations

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.:

AF XY:

0.383

AC XY:

28470

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.326

Hom.:

12440

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over