rs201157338
Positions:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_181426.2(CCDC39):āc.272A>Gā(p.Gln91Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000264 in 1,567,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0015 ( 1 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
CCDC39
NM_181426.2 missense
NM_181426.2 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 5.10
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008845836).
BP6
?
Variant 3-180661946-T-C is Benign according to our data. Variant chr3-180661946-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 525559.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}. Variant chr3-180661946-T-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00145 (221/152256) while in subpopulation AFR AF= 0.00505 (210/41574). AF 95% confidence interval is 0.00449. There are 1 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC39 | NM_181426.2 | c.272A>G | p.Gln91Arg | missense_variant | 3/20 | ENST00000476379.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC39 | ENST00000476379.6 | c.272A>G | p.Gln91Arg | missense_variant | 3/20 | 2 | NM_181426.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00144 AC: 219AN: 152138Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000377 AC: 68AN: 180156Hom.: 0 AF XY: 0.000221 AC XY: 21AN XY: 95118
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GnomAD4 exome AF: 0.000136 AC: 193AN: 1415710Hom.: 0 Cov.: 31 AF XY: 0.0000972 AC XY: 68AN XY: 699546
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GnomAD4 genome ? AF: 0.00145 AC: 221AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.00140 AC XY: 104AN XY: 74436
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 03, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Primary ciliary dyskinesia 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 11, 2023 | The CCDC39 c.272A>G; p.Gln91Arg variant (rs201157338), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 525559).This variant is found in the African/African-American population with an allele frequency of 0.54% (106/19700 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.247). While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;.
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at