rs779679242
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000156.6(GAMT):āc.312A>Gā(p.Pro104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,572,142 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000046 ( 0 hom. )
Consequence
GAMT
NM_000156.6 synonymous
NM_000156.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.31
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 19-1399808-T-C is Benign according to our data. Variant chr19-1399808-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 205565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.32 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAMT | NM_000156.6 | c.312A>G | p.Pro104= | synonymous_variant | 2/6 | ENST00000252288.8 | |
GAMT | NM_138924.3 | c.312A>G | p.Pro104= | synonymous_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAMT | ENST00000252288.8 | c.312A>G | p.Pro104= | synonymous_variant | 2/6 | 1 | NM_000156.6 | P1 | |
GAMT | ENST00000447102.8 | c.312A>G | p.Pro104= | synonymous_variant | 2/5 | 2 | |||
GAMT | ENST00000640762.1 | c.243A>G | p.Pro81= | synonymous_variant | 2/6 | 5 | |||
GAMT | ENST00000591788.3 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000701 AC: 13AN: 185556Hom.: 0 AF XY: 0.0000902 AC XY: 9AN XY: 99832
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GnomAD4 exome AF: 0.0000465 AC: 66AN: 1420072Hom.: 0 Cov.: 33 AF XY: 0.0000526 AC XY: 37AN XY: 702988
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 19, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Cerebral creatine deficiency syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at