12-110847068-G-T

Variant names:

• chr12-110847068-G-T
• rs2339635
• NM_152591.3:c.-134G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152591.3(CCDC63):​c.-134G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: CCDC63 NM_152591.3 5_prime_UTR_premature_start_codon_gain
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.-134G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_689804.1
	CCDC63	NM_152591.3	MANE Select	c.-134G>T		5_prime_UTR	Exon 1 of 12	NP_689804.1
	CCDC63	NM_001286243.2		c.-149G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001273172.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.43
PhyloP100		-1.5
PromoterAI		0.034	Neutral

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;