rs185157579
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_017950.4(CCDC40):c.1459G>A(p.Ala487Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,612,274 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.1459G>A | p.Ala487Thr | missense_variant | 10/20 | ENST00000397545.9 | |
LOC124904074 | XR_007065931.1 | n.305+5729C>T | intron_variant, non_coding_transcript_variant | ||||
CCDC40 | NM_001243342.2 | c.1459G>A | p.Ala487Thr | missense_variant | 10/18 | ||
CCDC40 | NM_001330508.2 | c.1459G>A | p.Ala487Thr | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.1459G>A | p.Ala487Thr | missense_variant | 10/20 | 5 | NM_017950.4 | P2 | |
ENST00000695611.1 | n.313+5729C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000271 AC: 41AN: 151298Hom.: 2 Cov.: 29
GnomAD3 exomes AF: 0.000474 AC: 118AN: 248710Hom.: 1 AF XY: 0.000451 AC XY: 61AN XY: 135248
GnomAD4 exome AF: 0.000164 AC: 240AN: 1460858Hom.: 1 Cov.: 32 AF XY: 0.000166 AC XY: 121AN XY: 726738
GnomAD4 genome ? AF: 0.000271 AC: 41AN: 151416Hom.: 2 Cov.: 29 AF XY: 0.000324 AC XY: 24AN XY: 73974
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at