3-180616931-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_181426.2(CCDC39):c.2301G>A(p.Leu767Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,483,642 control chromosomes in the GnomAD database, including 3,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L767L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.092 ( 1063 hom., cov: 32)

Exomes 𝑓: 0.045 ( 2099 hom. )

Consequence

CCDC39
NM_181426.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.742

Publications

7 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 links:

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TTC14 links:

ENSG00000145075 (HGNC:):

ENSG00000145075 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-180616931-C-T is Benign according to our data. Variant chr3-180616931-C-T is described in ClinVar as [Benign]. Clinvar id is 162840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.742 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC39	NM_181426.2 link	c.2301G>A	p.Leu767Leu	synonymous_variant	Exon 17 of 20	ENST00000476379.6	NP_852091.1	Q9UFE4-1
TTC14	NM_001288582.2 link	c.1775-449C>T		intron_variant	Intron 12 of 12		NP_001275511.1	Q96N46-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6 link	c.2301G>A	p.Leu767Leu	synonymous_variant	Exon 17 of 20	2	NM_181426.2	ENSP00000417960.2		Q9UFE4-1

Frequencies

GnomAD3 genomes

AF:

0.0921

AC:

13990

AN:

151942

Hom.:

1051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.0534

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.0824

Gnomad FIN

AF:

0.00728

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0852

GnomAD2 exomes

AF:

0.0556

AC:

11959

AN:

215174

AF XY:

0.0562

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00684

Gnomad NFE exome

AF:

0.0459

Gnomad OTH exome

AF:

0.0678

GnomAD4 exome

AF:

0.0450

AC:

59959

AN:

1331582

Hom.:

2099

Cov.:

AF XY:

0.0464

AC XY:

30909

AN XY:

665944

show subpopulations

African (AFR)

AF:

0.211

AC:

6279

AN:

29786

American (AMR)

AF:

0.0472

AC:

1909

AN:

40406

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

1273

AN:

24954

East Asian (EAS)

AF:

0.00101

AC:

AN:

38740

South Asian (SAS)

AF:

0.0829

AC:

6529

AN:

78760

European-Finnish (FIN)

AF:

0.00714

AC:

365

AN:

51130

Middle Eastern (MID)

AF:

0.107

AC:

589

AN:

5496

European-Non Finnish (NFE)

AF:

0.0395

AC:

39774

AN:

1006492

Other (OTH)

AF:

0.0574

AC:

3202

AN:

55818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

2111

4221

6332

8442

10553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1448

2896

4344

5792

7240

<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:

0.0923

AC:

14029

AN:

152060

Hom.:

1063

Cov.:

AF XY:

0.0890

AC XY:

6614

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.212

AC:

8796

AN:

41430

American (AMR)

AF:

0.0751

AC:

1147

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0534

AC:

185

AN:

3462

East Asian (EAS)

AF:

0.00289

AC:

AN:

5192

South Asian (SAS)

AF:

0.0817

AC:

394

AN:

4824

European-Finnish (FIN)

AF:

0.00728

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0453

AC:

3080

AN:

67980

Other (OTH)

AF:

0.0862

AC:

182

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

628

1256

1883

2511

3139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0617

Hom.:

459

Bravo

AF:

0.101

Asia WGS

AF:

0.0730

AC:

252

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu767Leu in exon 17 of CCDC39: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 20.2% (724/3588) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11914833). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 26, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 21, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia 14

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

(source)

DANN

Benign

0.53

PhyloP100

0.74

PromoterAI

-0.0099

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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