chr19-1399536-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000156.6(GAMT):c.379G>A(p.Gly127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000156.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GAMT | NM_000156.6 | c.379G>A | p.Gly127Ser | missense_variant | 3/6 | ENST00000252288.8 | NP_000147.1 | |
GAMT | NM_138924.3 | c.379G>A | p.Gly127Ser | missense_variant | 3/5 | NP_620279.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GAMT | ENST00000252288.8 | c.379G>A | p.Gly127Ser | missense_variant | 3/6 | 1 | NM_000156.6 | ENSP00000252288.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000443 AC: 11AN: 248576Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134758
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460708Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 726536
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74464
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 22, 2015 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Cerebral creatine deficiency syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2021 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 127 of the GAMT protein (p.Gly127Ser). This variant is present in population databases (rs570476209, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 205567). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Deficiency of guanidinoacetate methyltransferase Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at