rs201485243
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020549.5(CHAT):c.1771G>A(p.Val591Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_020549.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHAT | NM_020549.5 | c.1771G>A | p.Val591Met | missense_variant | 12/15 | ENST00000337653.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHAT | ENST00000337653.7 | c.1771G>A | p.Val591Met | missense_variant | 12/15 | 1 | NM_020549.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251174Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135824
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461678Hom.: 0 Cov.: 37 AF XY: 0.0000454 AC XY: 33AN XY: 727132
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74354
ClinVar
Submissions by phenotype
Familial infantile myasthenia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces valine with methionine at codon 591 of the CHAT protein (p.Val591Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs201485243, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with CHAT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | Revvity Omics, Revvity | Jan 10, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.1771G>A (p.V591M) alteration is located in exon 12 (coding exon 12) of the CHAT gene. This alteration results from a G to A substitution at nucleotide position 1771, causing the valine (V) at amino acid position 591 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 17, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at