rs73051767

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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 14

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	NM_181426.2	MANE Select	c.1528-43A>G		intron	N/A	NP_852091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.1528-43A>G		intron	N/A	ENSP00000417960.2
	CCDC39	ENST00000936067.1		c.1435-43A>G		intron	N/A	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.1336-43A>G		intron	N/A	ENSP00000499175.1

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

African (AFR) AF: 0.380 AC: 8810 AN: 23214

American (AMR) AF: 0.0652 AC: 1328 AN: 20366

Ashkenazi Jewish (ASJ) AF: 0.0460 AC: 992 AN: 21560

East Asian (EAS) AF: 0.00102 AC: 34 AN: 33306

South Asian (SAS) AF: 0.0787 AC: 4900 AN: 62238

European-Finnish (FIN) AF: 0.00654 AC: 250 AN: 38244

Middle Eastern (MID) AF: 0.0907 AC: 325 AN: 3582

European-Non Finnish (NFE) AF: 0.0411 AC: 33927 AN: 825560

Other (OTH) 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

African (AFR) AF: 0.364 AC: 15092 AN: 41488

American (AMR) AF: 0.0837 AC: 1280 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 163 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5192

South Asian (SAS) AF: 0.0756 AC: 365 AN: 4826

European-Finnish (FIN) AF: 0.00707 AC: 75 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0424 AC: 2883 AN: 67994

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.0940 Hom.: 231

Bravo AF: 0.150

Asia WGS AF: 0.0670 AC: 235 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		-0.89
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

Other links and lift over

dbSNP: rs73051767; hg19: chr3-180362088;