rs202027034

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181426.2(CCDC39):​c.2615C>T​(p.Thr872Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC39
NM_181426.2 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.771
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044492543).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC39NM_181426.2 linkc.2615C>T p.Thr872Ile missense_variant Exon 19 of 20 ENST00000476379.6 NP_852091.1 Q9UFE4-1
TTC14NM_001288582.2 linkc.1775-1045G>A 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.2615C>T p.Thr872Ile missense_variant Exon 19 of 20 2 NM_181426.2 ENSP00000417960.2 Q9UFE4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1460962
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726756
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
1.0
DANN
Benign
0.81
DEOGEN2
Benign
0.0016
.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.54
T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.044
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
.;M
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.0
D;N
REVEL
Benign
0.14
Sift
Uncertain
0.011
D;D
Sift4G
Uncertain
0.040
D;T
Polyphen
0.0010
.;B
Vest4
0.055
MutPred
0.20
.;Loss of loop (P = 0.0022);
MVP
0.14
MPC
0.11
ClinPred
0.086
T
GERP RS
-0.74
Varity_R
0.047

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-180334123; API