15-101177504-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014918.5(CHSY1):c.2293G>A(p.Gly765Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G765A) has been classified as Uncertain significance.
Frequency
Consequence
NM_014918.5 missense
Scores
Clinical Significance
Conservation
Publications
- temtamy preaxial brachydactyly syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHSY1 | ENST00000254190.4 | c.2293G>A | p.Gly765Arg | missense_variant | Exon 3 of 3 | 1 | NM_014918.5 | ENSP00000254190.3 | ||
CHSY1 | ENST00000543813.2 | n.*1608G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | ENSP00000496160.1 | ||||
CHSY1 | ENST00000543813.2 | n.*1608G>A | 3_prime_UTR_variant | Exon 3 of 3 | 2 | ENSP00000496160.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00 AC: 0AN: 251290 AF XY: 0.00
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461014Hom.: 0 Cov.: 66 AF XY: 0.00000275 AC XY: 2AN XY: 726634 show subpopulations
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74346 show subpopulations
ClinVar
Submissions by phenotype
Temtamy preaxial brachydactyly syndrome Uncertain:1
Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This sequence change replaces glycine with arginine at codon 765 of the CHSY1 protein (p.Gly765Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHSY1-related conditions. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at