rs201709592
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_017950.4(CCDC40):āc.334A>Gā(p.Thr112Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,614,104 control chromosomes in the GnomAD database, including 16 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T112K) has been classified as Uncertain significance.
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.334A>G | p.Thr112Ala | missense_variant | 3/20 | ENST00000397545.9 | |
CCDC40 | NM_001243342.2 | c.334A>G | p.Thr112Ala | missense_variant | 3/18 | ||
CCDC40 | NM_001330508.2 | c.334A>G | p.Thr112Ala | missense_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.334A>G | p.Thr112Ala | missense_variant | 3/20 | 5 | NM_017950.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00248 AC: 378AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00236 AC: 585AN: 248092Hom.: 4 AF XY: 0.00250 AC XY: 337AN XY: 134734
GnomAD4 exome AF: 0.00413 AC: 6036AN: 1461762Hom.: 16 Cov.: 33 AF XY: 0.00399 AC XY: 2900AN XY: 727212
GnomAD4 genome ? AF: 0.00249 AC: 379AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.00238 AC XY: 177AN XY: 74496
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 15 Uncertain:1Benign: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. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 09, 2023 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 12, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 06, 2015 | p.Thr112Ala in exon 3 of CCDC40: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (200/66682) of European chrom osomes, including 3 homozygotes, by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs201709592). - |
Primary ciliary dyskinesia Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2016 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | CCDC40: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at