Genetic Variant CCDC39:n.222G>C (chr3-180679648-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000650889.1(CCDC39):n.222G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 632,790 control chromosomes in the GnomAD database, including 516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 380 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 136 hom. )

Consequence

CCDC39
ENST00000650889.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.912

Publications

2 publications found

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:

CCDC39-AS1 (HGNC:41089): (CCDC39 antisense RNA 1)

CCDC39-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-180679648-C-G is Benign according to our data. Variant chr3-180679648-C-G is described in ClinVar as Benign. ClinVar VariationId is 1260646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650889.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	NM_181426.2	MANE Select	c.-268G>C		upstream_gene	N/A	NP_852091.1	Q9UFE4-1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
CCDC39	ENST00000650889.1	n.222G>C	non_coding_transcript_exon	Exon 2 of 12
ENSG00000145075	ENST00000651576.1	n.830G>C	non_coding_transcript_exon	Exon 6 of 25
CCDC39	ENST00000651818.1	n.192G>C	non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes

AF:

0.0377

AC:

5741

AN:

152142

Hom.:

375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.00769

AC:

1062

AN:

138034

AF XY:

0.00590

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.00502

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000948

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000349

Gnomad OTH exome

AF:

0.00426

GnomAD4 exome

AF:

0.00521

AC:

2503

AN:

480530

Hom.:

136

Cov.:

AF XY:

0.00411

AC XY:

1078

AN XY:

262500

show subpopulations

African (AFR)

AF:

0.130

AC:

1856

AN:

14282

American (AMR)

AF:

0.00646

AC:

209

AN:

32374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17730

East Asian (EAS)

AF:

0.0000788

AC:

AN:

25392

South Asian (SAS)

AF:

0.00153

AC:

AN:

61384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26906

Middle Eastern (MID)

AF:

0.00244

AC:

AN:

3682

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

272610

Other (OTH)

AF:

0.0104

AC:

273

AN:

26170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0379

AC:

5774

AN:

152260

Hom.:

380

Cov.:

AF XY:

0.0358

AC XY:

2662

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.133

AC:

5505

AN:

41522

American (AMR)

AF:

0.0122

AC:

187

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68018

Other (OTH)

AF:

0.0241

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

244

488

731

975

1219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0202

Hom.:

Bravo

AF:

0.0437

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.1

(source)

DANN

Benign

0.38

PhyloP100

-0.91

PromoterAI

-0.021

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over