rs147028259

chr3-180619381-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_181426.2(CCDC39):c.2159-16A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,247,156 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (11 hom., cov: 32)
  • Exomes 𝑓: 0.011 (87 hom.)
• Consequence: CCDC39 NM_181426.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0570

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=-0.83).
• BP6: Variant 3-180619381-T-G is Benign according to our data. Variant chr3-180619381-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 262967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0083 (1264/152236) while in subpopulation NFE AF= 0.0132 (899/67994). AF 95% confidence interval is 0.0125. There are 11 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC39	NM_181426.2	c.2159-16A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000476379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC39	ENST00000476379.6	c.2159-16A>C		splice_polypyrimidine_tract_variant, intron_variant		2	NM_181426.2	P2

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1264 AN: 152118 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.00695

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00858

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00875 AC: 1190 AN: 136006 Hom.: 5 AF XY: 0.00831 AC XY: 594 AN XY: 71510

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.00922

Gnomad ASJ exome AF: 0.00216

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00304

Gnomad FIN exome AF: 0.00930

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.00954

GnomAD4 exome AF: 0.0110 AC: 12014 AN: 1094920 Hom.: 87 Cov.: 14 AF XY: 0.0107 AC XY: 5913 AN XY: 552804

Gnomad4 AFR exome AF: 0.00201

Gnomad4 AMR exome AF: 0.00822

Gnomad4 ASJ exome AF: 0.00198

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00306

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.00830 AC: 1264 AN: 152236 Hom.: 11 Cov.: 32 AF XY: 0.00758 AC XY: 564 AN XY: 74436

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00694

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00858

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00961 Hom.: 4

Bravo AF: 0.00780

Asia WGS AF: 0.000867 AC: 3 AN: 3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

Mar 28, 2016

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Primary ciliary dyskinesia 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.2
Dann	Benign	0.68

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: rs147028259; hg19: chr3-180337169;