3-180631612-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181426.2(CCDC39):​c.1875-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,589,300 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00044 ( 5 hom. )

Consequence

CCDC39
NM_181426.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.756

Publications

0 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 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

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=-0.87).
BP6
Variant 3-180631612-C-T is Benign according to our data. Variant chr3-180631612-C-T is described in ClinVar as [Benign]. Clinvar id is 262965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00434 (661/152228) while in subpopulation AFR AF = 0.015 (623/41540). AF 95% confidence interval is 0.014. There are 8 homozygotes in GnomAd4. There are 295 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC39NM_181426.2 linkc.1875-20G>A intron_variant Intron 13 of 19 ENST00000476379.6 NP_852091.1 Q9UFE4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC39ENST00000476379.6 linkc.1875-20G>A intron_variant Intron 13 of 19 2 NM_181426.2 ENSP00000417960.2 Q9UFE4-1

Frequencies

GnomAD3 genomes
AF:
0.00435
AC:
661
AN:
152110
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0150
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00431
GnomAD2 exomes
AF:
0.00113
AC:
246
AN:
218262
AF XY:
0.000801
show subpopulations
Gnomad AFR exome
AF:
0.0159
Gnomad AMR exome
AF:
0.000621
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000100
Gnomad OTH exome
AF:
0.000180
GnomAD4 exome
AF:
0.000439
AC:
631
AN:
1437072
Hom.:
5
Cov.:
28
AF XY:
0.000391
AC XY:
279
AN XY:
714384
show subpopulations
African (AFR)
AF:
0.0166
AC:
544
AN:
32822
American (AMR)
AF:
0.000747
AC:
31
AN:
41522
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25866
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39468
South Asian (SAS)
AF:
0.0000120
AC:
1
AN:
83510
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45142
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5742
European-Non Finnish (NFE)
AF:
0.00000725
AC:
8
AN:
1103260
Other (OTH)
AF:
0.000787
AC:
47
AN:
59740
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
28
56
83
111
139
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00434
AC:
661
AN:
152228
Hom.:
8
Cov.:
32
AF XY:
0.00396
AC XY:
295
AN XY:
74430
show subpopulations
African (AFR)
AF:
0.0150
AC:
623
AN:
41540
American (AMR)
AF:
0.00164
AC:
25
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000588
AC:
4
AN:
68012
Other (OTH)
AF:
0.00427
AC:
9
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
31
62
94
125
156
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00231
Hom.:
1
Bravo
AF:
0.00509
Asia WGS
AF:
0.000289
AC:
2
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

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
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Primary ciliary dyskinesia 14 Benign:1
May 20, 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
-0.87
CADD
Benign
1.0
DANN
Benign
0.68
PhyloP100
-0.76
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs73051759; hg19: chr3-180349400; API