3-180647255-TAA-TA

Position:

• chr3-180647255-TAA-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_181426.2(CCDC39):​c.1363-13del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,152,244 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 29)
  • Exomes 𝑓: 0.031 (4 hom.)
• Consequence: CCDC39 NM_181426.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.273

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 3-180647255-TA-T is Benign according to our data. Variant chr3-180647255-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 344268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-180647255-TA-T is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC39	NM_181426.2	c.1363-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000476379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC39	ENST00000476379.6	c.1363-13del		splice_polypyrimidine_tract_variant, intron_variant		2	NM_181426.2	P2

Frequencies

GnomAD3 genomes AF: 0.00370 AC: 534 AN: 144342 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000298

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00213

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000792

Gnomad OTH AF: 0.00204

GnomAD4 exome AF: 0.0313 AC: 31548 AN: 1007838 Hom.: 4 Cov.: 24 AF XY: 0.0323 AC XY: 15971 AN XY: 493986

Gnomad4 AFR exome AF: 0.0554

Gnomad4 AMR exome AF: 0.0538

Gnomad4 ASJ exome AF: 0.0465

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.0307

Gnomad4 NFE exome AF: 0.0276

Gnomad4 OTH exome AF: 0.0363

GnomAD4 genome AF: 0.00370 AC: 534 AN: 144406 Hom.: 1 Cov.: 29 AF XY: 0.00321 AC XY: 225 AN XY: 70034

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000298

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000218

Gnomad4 FIN AF: 0.00213

Gnomad4 NFE AF: 0.000792

Gnomad4 OTH AF: 0.00203

Alfa AF: 0.0450 Hom.: 89

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Primary ciliary dyskinesia 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs374074877; hg19: chr3-180365043;