19-1399597-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000156.6(GAMT):c.328-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
GAMT
NM_000156.6 intron
NM_000156.6 intron
Scores
2
Splicing: ADA: 0.003284
2
Clinical Significance
Conservation
PhyloP100: 0.264
Publications
0 publications found
Genes affected
GAMT (HGNC:4136): (guanidinoacetate N-methyltransferase) The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene. Pseudogenes of this gene are found on chromosomes 2 and 13. [provided by RefSeq, Feb 2012]
GAMT Gene-Disease associations (from GenCC):
- guanidinoacetate methyltransferase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000156.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GAMT | NM_000156.6 | MANE Select | c.328-10C>G | intron | N/A | NP_000147.1 | |||
| GAMT | NM_138924.3 | c.328-10C>G | intron | N/A | NP_620279.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GAMT | ENST00000252288.8 | TSL:1 MANE Select | c.328-10C>G | intron | N/A | ENSP00000252288.1 | |||
| GAMT | ENST00000640164.1 | TSL:2 | n.151C>G | non_coding_transcript_exon | Exon 1 of 4 | ||||
| GAMT | ENST00000447102.8 | TSL:2 | c.328-10C>G | intron | N/A | ENSP00000403536.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000407 AC: 1AN: 245432 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
245432
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459154Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725740 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1459154
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
725740
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33434
American (AMR)
AF:
AC:
0
AN:
44512
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26070
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
85900
European-Finnish (FIN)
AF:
AC:
0
AN:
52384
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111080
Other (OTH)
AF:
AC:
0
AN:
60326
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Deficiency of guanidinoacetate methyltransferase Uncertain:1
Feb 19, 2025
Natera, Inc.
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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