NM_181426.2:c.1363-3delC

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_181426.2(CCDC39):c.1363-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,558,374 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 3 hom. )

Consequence

CCDC39
NM_181426.2 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

Conservation

PhyloP100: 3.55

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CCDC39 links:

ENSG00000145075 (HGNC:):

ENSG00000145075 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 3-180647245-TG-T is Benign according to our data. Variant chr3-180647245-TG-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 242168.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00193 (288/149096) while in subpopulation AMR AF = 0.00555 (82/14764). AF 95% confidence interval is 0.00458. There are 0 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC39	NM_181426.2 link	c.1363-3delC		splice_region_variant, 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.1363-3delC		splice_region_variant, intron_variant	Intron 10 of 19	2	NM_181426.2	ENSP00000417960.2		Q9UFE4-1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

290

AN:

148984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0196

Gnomad NFE

AF:

0.000614

Gnomad OTH

AF:

0.00493

GnomAD2 exomes

AF:

0.00124

AC:

215

AN:

173520

AF XY:

0.00123

show subpopulations

Gnomad AFR exome

AF:

0.00383

Gnomad AMR exome

AF:

0.00455

Gnomad ASJ exome

AF:

0.000530

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000113

Gnomad NFE exome

AF:

0.000829

Gnomad OTH exome

AF:

0.00211

GnomAD4 exome

AF:

0.000727

AC:

1025

AN:

1409278

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

526

AN XY:

698472

show subpopulations

African (AFR)

AF:

0.00447

AC:

138

AN:

30886

American (AMR)

AF:

0.00394

AC:

126

AN:

31940

Ashkenazi Jewish (ASJ)

AF:

0.000573

AC:

AN:

24434

East Asian (EAS)

AF:

0.00

AC:

AN:

38920

South Asian (SAS)

AF:

0.0000648

AC:

AN:

77218

European-Finnish (FIN)

AF:

0.0000392

AC:

AN:

50956

Middle Eastern (MID)

AF:

0.00681

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.000534

AC:

583

AN:

1091036

Other (OTH)

AF:

0.00204

AC:

119

AN:

58310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00193

AC:

288

AN:

149096

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

156

AN XY:

72722

show subpopulations

African (AFR)

AF:

0.00359

AC:

147

AN:

41000

American (AMR)

AF:

0.00555

AC:

AN:

14764

Ashkenazi Jewish (ASJ)

AF:

0.000292

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000212

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10034

Middle Eastern (MID)

AF:

0.0211

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000614

AC:

AN:

66756

Other (OTH)

AF:

0.00487

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000656

Hom.:

Bravo

AF:

0.00253

Asia WGS

AF:

0.000869

AC:

AN:

3468

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CCDC39: BP4, BS2 -

Oct 28, 2019

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 21131972, 22693285) -

Primary ciliary dyskinesia

Benign:2

Feb 06, 2017

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 14

Uncertain:1

Mar 04, 2021

New York Genome Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 14, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.1363-3delC: This variant is not expected to have clinical significance because it has been identified in 0.35% (17/4804) of Latino chromosomes and 0.34% (22/6 500) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs551191744). -

CCDC39-related disorder

Benign:1

Jun 16, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.5

Mutation Taster

=9/91

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over