Genetic Variant NM_181426.2:c.1528-43A>G (chr3-180644300-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181426.2(CCDC39):c.1528-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 1,227,150 control chromosomes in the GnomAD database, including 5,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2911 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2906 hom. )

Consequence

CCDC39
NM_181426.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.888

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-180644300-T-C is Benign according to our data. Variant chr3-180644300-T-C is described in ClinVar as [Benign]. Clinvar id is 262962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC39	NM_181426.2 link	c.1528-43A>G		intron_variant	Intron 11 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.1528-43A>G		intron_variant	Intron 11 of 19	2	NM_181426.2	ENSP00000417960.2		Q9UFE4-1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20221

AN:

152066

Hom.:

2903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0840

Gnomad ASJ

AF:

0.0469

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.0762

Gnomad FIN

AF:

0.00707

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0425

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0666

AC:

7029

AN:

105554

Hom.:

617

AF XY:

0.0624

AC XY:

3567

AN XY:

57162

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.0666

Gnomad ASJ exome

AF:

0.0494

Gnomad EAS exome

AF:

0.00237

Gnomad SAS exome

AF:

0.0782

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0684

GnomAD4 exome

AF:

0.0499

AC:

53670

AN:

1074966

Hom.:

2906

Cov.:

AF XY:

0.0502

AC XY:

27154

AN XY:

541334

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.0652

Gnomad4 ASJ exome

AF:

0.0460

Gnomad4 EAS exome

AF:

0.00102

Gnomad4 SAS exome

AF:

0.0787

Gnomad4 FIN exome

AF:

0.00654

Gnomad4 NFE exome

AF:

0.0411

Gnomad4 OTH exome

AF:

0.0662

GnomAD4 genome

AF:

0.133

AC:

20250

AN:

152184

Hom.:

2911

Cov.:

AF XY:

0.128

AC XY:

9532

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.0837

Gnomad4 ASJ

AF:

0.0469

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0756

Gnomad4 FIN

AF:

0.00707

Gnomad4 NFE

AF:

0.0424

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0940

Hom.:

231

Bravo

AF:

0.150

Asia WGS

AF:

0.0670

AC:

235

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

This variant is associated with the following publications: (PMID: 23891469) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 14

Benign:1

Nov 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.9

DANN

Benign

0.79

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