chr3-180616835-C-T

Position:

chr3-180616835-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_181426.2(CCDC39):c.2397G>A(p.Val799=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,606,498 control chromosomes in the GnomAD database, including 31,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2813 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28860 hom. )

Consequence

CCDC39
NM_181426.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.448

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 3-180616835-C-T is Benign according to our data. Variant chr3-180616835-C-T is described in ClinVar as [Benign]. Clinvar id is 162839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-180616835-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.448 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC39	NM_181426.2 linkuse as main transcript	c.2397G>A	p.Val799=	synonymous_variant	17/20	ENST00000476379.6	NP_852091.1
TTC14	NM_001288582.2 linkuse as main transcript	c.1775-545C>T		intron_variant			NP_001275511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6 linkuse as main transcript	c.2397G>A	p.Val799=	synonymous_variant	17/20	2	NM_181426.2	ENSP00000417960	P2	Q9UFE4-1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28153

AN:

151998

Hom.:

2810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.176

AC:

43280

AN:

246428

Hom.:

4229

AF XY:

0.174

AC XY:

23216

AN XY:

133752

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.00145

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.194

AC:

282625

AN:

1454382

Hom.:

28860

Cov.:

AF XY:

0.192

AC XY:

138607

AN XY:

723594

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.00106

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.182

GnomAD4 genome

AF:

0.185

AC:

28177

AN:

152116

Hom.:

2813

Cov.:

AF XY:

0.185

AC XY:

13778

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.193

Hom.:

2020

Bravo

AF:

0.179

Asia WGS

AF:

0.0600

AC:

211

AN:

3476

EpiCase

AF:

0.202

EpiControl

AF:

0.198

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Val799Val 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 19.5% (1589/8130) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs7612917). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 2016	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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Primary ciliary dyskinesia 14

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

-0.52

CADD

Benign

2.5

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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