rs371071557
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_017950.4(CCDC40):c.1105G>A(p.Ala369Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000631 in 1,600,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017950.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.1105G>A | p.Ala369Thr | missense_variant | 7/20 | ENST00000397545.9 | NP_060420.2 | |
CCDC40 | NM_001243342.2 | c.1105G>A | p.Ala369Thr | missense_variant | 7/18 | NP_001230271.1 | ||
CCDC40 | NM_001330508.2 | c.1105G>A | p.Ala369Thr | missense_variant | 7/11 | NP_001317437.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.1105G>A | p.Ala369Thr | missense_variant | 7/20 | 5 | NM_017950.4 | ENSP00000380679.4 |
Frequencies
GnomAD3 genomes AF: 0.0000857 AC: 13AN: 151772Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000184 AC: 41AN: 222580Hom.: 0 AF XY: 0.000156 AC XY: 19AN XY: 122122
GnomAD4 exome AF: 0.0000607 AC: 88AN: 1448704Hom.: 0 Cov.: 34 AF XY: 0.0000611 AC XY: 44AN XY: 720080
GnomAD4 genome AF: 0.0000857 AC: 13AN: 151772Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74114
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 19, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 369 of the CCDC40 protein (p.Ala369Thr). This variant is present in population databases (rs371071557, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CCDC40-related conditions. ClinVar contains an entry for this variant (Variation ID: 566968). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CCDC40 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 02, 2024 | This alteration is classified as 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 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at