chr12-110902439-T-C

Variant names:

• chr12-110902439-T-C
• rs10774610
• NM_152591.3:c.1343-2149T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152591.3. 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.1343-2149T>C		intron	N/A	NP_689804.1
	CCDC63	NM_001286243.2		c.1223-2149T>C		intron	N/A	NP_001273172.1
	CCDC63	NM_001286244.2		c.1106-2149T>C		intron	N/A	NP_001273173.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC63	ENST00000308208.10	TSL:2 MANE Select	c.1343-2149T>C		intron	N/A	ENSP00000312399.5
	CCDC63	ENST00000552694.1	TSL:1	c.1106-2149T>C		intron	N/A	ENSP00000450217.1
	CCDC63	ENST00000545036.5	TSL:2	c.1223-2149T>C		intron	N/A	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

African (AFR) AF: 0.412 AC: 17078 AN: 41432

American (AMR) AF: 0.357 AC: 5443 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1126 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4818

European-Finnish (FIN) AF: 0.387 AC: 4091 AN: 10564

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22643 AN: 67934

Other (OTH) AF: 0.301 AC: 636 AN: 2110

Alfa AF: 0.329 Hom.: 34772

Bravo AF: 0.353

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.28
DANN	Benign	0.72
PhyloP100		-1.0
Mutation Taster		=100/0	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: rs10774610; hg19: chr12-111340243;