19-1398977-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000156.6(GAMT):c.509A>C(p.Asn170Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,024 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. N170S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000156.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAMT | NM_000156.6 | c.509A>C | p.Asn170Thr | missense_variant | 5/6 | ENST00000252288.8 | |
GAMT | NM_138924.3 | c.509A>C | p.Asn170Thr | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAMT | ENST00000252288.8 | c.509A>C | p.Asn170Thr | missense_variant | 5/6 | 1 | NM_000156.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151876Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250906Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135824
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461148Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726874
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151876Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74198
ClinVar
Submissions by phenotype
Cerebral creatine deficiency syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 04, 2022 | This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 170 of the GAMT protein (p.Asn170Thr). This variant is present in population databases (rs202199674, gnomAD 0.009%). 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: 664322). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 10, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at