rs200902434
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting
The NM_017950.4(CCDC40):c.3176G>A(p.Arg1059Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,613,922 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★★).
Frequency
Consequence
NM_017950.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC40 | NM_017950.4 | c.3176G>A | p.Arg1059Gln | missense_variant | 19/20 | ENST00000397545.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC40 | ENST00000397545.9 | c.3176G>A | p.Arg1059Gln | missense_variant | 19/20 | 5 | NM_017950.4 | P2 | |
CCDC40 | ENST00000574799.5 | n.2713G>A | non_coding_transcript_exon_variant | 15/16 | 1 | ||||
CCDC40 | ENST00000572253.5 | n.3427G>A | non_coding_transcript_exon_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000112 AC: 28AN: 249054Hom.: 1 AF XY: 0.000133 AC XY: 18AN XY: 135282
GnomAD4 exome AF: 0.0000800 AC: 117AN: 1461592Hom.: 2 Cov.: 35 AF XY: 0.0000949 AC XY: 69AN XY: 727082
GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74490
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1059 of the CCDC40 protein (p.Arg1059Gln). This variant is present in population databases (rs200902434, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. 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: 525411). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | The c.3176G>A (p.R1059Q) alteration is located in exon 19 (coding exon 19) of the CCDC40 gene. This alteration results from a G to A substitution at nucleotide position 3176, causing the arginine (R) at amino acid position 1059 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
CCDC40-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 08, 2023 | The CCDC40 c.3176G>A variant is predicted to result in the amino acid substitution p.Arg1059Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-78071198-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Primary ciliary dyskinesia 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 21, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at