3-180679690-A-G

Variant names:

• chr3-180679690-A-G
• rs147114975
• ENST00000650889.1:n.180T>C

Variant summary

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

The ENST00000650889.1(CCDC39):​n.180T>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 0.00000244 in 409,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: CCDC39 ENST00000650889.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 0 publications found

Genes affected

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

ENSG00000145075 (HGNC:):

CCDC39-AS1 (HGNC:41089): (CCDC39 antisense RNA 1)

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=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650889.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	NM_181426.2	MANE Select	c.-310T>C		upstream_gene	N/A	NP_852091.1	Q9UFE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000650889.1		n.180T>C		non_coding_transcript_exon	Exon 2 of 12
	ENSG00000145075	ENST00000651576.1		n.788T>C		non_coding_transcript_exon	Exon 6 of 25
	CCDC39	ENST00000651818.1		n.150T>C		non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000244 AC: 1 AN: 409440 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 226374

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12546

American (AMR) AF: 0.00 AC: 0 AN: 30324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15152

East Asian (EAS) AF: 0.00 AC: 0 AN: 18158

South Asian (SAS) AF: 0.00 AC: 0 AN: 60710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20234

Middle Eastern (MID) AF: 0.000302 AC: 1 AN: 3312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 227360

Other (OTH) AF: 0.00 AC: 0 AN: 21644

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		-0.64
PromoterAI		-0.028	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147114975; hg19: chr3-180397478;