rs73051767

Positions:

• chr3-180644300-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.888

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]

ACMG classification

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/exons	MANE	UniProt
CCDC39	NM_181426.2	c.1528-43A>G		intron_variant		ENST00000476379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC39	ENST00000476379.6	c.1528-43A>G		intron_variant		2	NM_181426.2	P2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20221 AN: 152066 Hom.: 2903 Cov.: 32

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

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.: 15 AF XY: 0.0502 AC XY: 27154 AN XY: 541334

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.: 32 AF XY: 0.128 AC XY: 9532 AN XY: 74418

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 28, 2023

- -

Primary ciliary dyskinesia 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 31, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 21, 2019

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

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

Other links and lift over

dbSNP: rs73051767; hg19: chr3-180362088;