3-180644300-T-C

Variant names:

• chr3-180644300-T-C
• rs73051767
• NM_181426.2:c.1528-43A>G

Variant summary

Our verdict is Benign. The variant received -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:5
• 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]

ENSG00000145075 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.1528-43A>G		intron_variant	Intron 11 of 19	ENST00000476379.6	NP_852091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6	c.1528-43A>G		intron_variant	Intron 11 of 19	2	NM_181426.2	ENSP00000417960.2

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

GnomAD2 exomes AF: 0.0666 AC: 7029 AN: 105554 AF XY: 0.0624

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 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 AC: 8810 AN: 23214

Gnomad4 AMR exome AF: 0.0652 AC: 1328 AN: 20366

Gnomad4 ASJ exome AF: 0.0460 AC: 992 AN: 21560

Gnomad4 EAS exome AF: 0.00102 AC: 34 AN: 33306

Gnomad4 SAS exome AF: 0.0787 AC: 4900 AN: 62238

Gnomad4 FIN exome AF: 0.00654 AC: 250 AN: 38244

Gnomad4 NFE exome AF: 0.0411 AC: 33927 AN: 825560

Gnomad4 Remaining exome AF: 0.0662 AC: 3104 AN: 46896

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 AC: 0.363768 AN: 0.363768

Gnomad4 AMR AF: 0.0837 AC: 0.0837258 AN: 0.0837258

Gnomad4 ASJ AF: 0.0469 AC: 0.046947 AN: 0.046947

Gnomad4 EAS AF: 0.00289 AC: 0.00288906 AN: 0.00288906

Gnomad4 SAS AF: 0.0756 AC: 0.075632 AN: 0.075632

Gnomad4 FIN AF: 0.00707 AC: 0.00707014 AN: 0.00707014

Gnomad4 NFE AF: 0.0424 AC: 0.0424008 AN: 0.0424008

Gnomad4 OTH AF: 0.113 AC: 0.11327 AN: 0.11327

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

Submissions by phenotype

not provided Benign:2

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) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
Mutation Taster		=100/0	polymorphism (auto)

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;