Genetic Variant CCDC39:c.1363-13delT (chr3-180647255-TA-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_181426.2(CCDC39):c.1363-13delT variant causes a 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 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.273

Variant links:

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]

CCDC39 links:

ENSG00000145075 (HGNC:):

ENSG00000145075 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CCDC39	NM_181426.2 link	c.1363-13delT		intron_variant	Intron 10 of 19	ENST00000476379.6	NP_852091.1	Q9UFE4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6 link	c.1363-13delT		intron_variant	Intron 10 of 19	2	NM_181426.2	ENSP00000417960.2		Q9UFE4-1

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

534

AN:

144342

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0323

AC XY:

15971

AN XY:

493986

show subpopulations

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.:

Cov.:

AF XY:

0.00321

AC XY:

225

AN XY:

70034

show subpopulations

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.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:2

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 14

Benign:1

Apr 08, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over