rs144790394
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000481.4(AMT):c.555C>T(p.Pro185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,740 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
AMT
NM_000481.4 synonymous
NM_000481.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.13
Genes affected
AMT (HGNC:473): (aminomethyltransferase) This gene encodes one of four critical components of the glycine cleavage system. Mutations in this gene have been associated with glycine encephalopathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 3-49419401-G-A is Benign according to our data. Variant chr3-49419401-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 553783.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=1.13 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMT | NM_000481.4 | c.555C>T | p.Pro185= | synonymous_variant | 6/9 | ENST00000273588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMT | ENST00000273588.9 | c.555C>T | p.Pro185= | synonymous_variant | 6/9 | 1 | NM_000481.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000724 AC: 18AN: 248746Hom.: 0 AF XY: 0.0000890 AC XY: 12AN XY: 134766
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GnomAD4 exome AF: 0.000248 AC: 363AN: 1461546Hom.: 0 Cov.: 31 AF XY: 0.000231 AC XY: 168AN XY: 727078
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74348
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Non-ketotic hyperglycinemia Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 15, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 15, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
AMT-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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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