chr7-100893829-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000665.5(ACHE):āc.404C>Gā(p.Pro135Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,802 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P135A) has been classified as Likely benign.
Frequency
Consequence
NM_000665.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACHE | NM_000665.5 | c.404C>G | p.Pro135Arg | missense_variant | 2/5 | ENST00000241069.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACHE | ENST00000241069.11 | c.404C>G | p.Pro135Arg | missense_variant | 2/5 | 1 | NM_000665.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249782Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134920
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460672Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726550
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2023 | The c.404C>G (p.P135R) alteration is located in exon 2 (coding exon 1) of the ACHE gene. This alteration results from a C to G substitution at nucleotide position 404, causing the proline (P) at amino acid position 135 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at