3-180616704-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_181426.2(CCDC39):​c.2407-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC39
NM_181426.2 intron

Scores

2
Splicing: ADA: 0.003337
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71

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]
TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 3-180616704-A-G is Benign according to our data. Variant chr3-180616704-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 242173.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC39NM_181426.2 linkc.2407-9T>C intron_variant Intron 17 of 19 ENST00000476379.6 NP_852091.1 Q9UFE4-1
TTC14NM_001288582.2 linkc.1775-676A>G intron_variant Intron 12 of 12 NP_001275511.1 Q96N46-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC39ENST00000476379.6 linkc.2407-9T>C intron_variant Intron 17 of 19 2 NM_181426.2 ENSP00000417960.2 Q9UFE4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1430802
Hom.:
0
Cov.:
30
AF XY:
0.00000141
AC XY:
1
AN XY:
709450
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32764
American (AMR)
AF:
0.0000499
AC:
2
AN:
40068
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25504
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38880
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82382
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51488
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5700
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1094882
Other (OTH)
AF:
0.00
AC:
0
AN:
59134
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Jan 22, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.63
CADD
Benign
20
DANN
Benign
0.78
PhyloP100
1.7
PromoterAI
0.0033
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0033
dbscSNV1_RF
Benign
0.040
SpliceAI score (max)
0.13
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: rs878855282; hg19: chr3-180334492; API