rs4703772
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_001713.3(BHMT):c.792C>T(p.Leu264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 1,613,508 control chromosomes in the GnomAD database, including 969 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.012 ( 135 hom., cov: 32)
Exomes 𝑓: 0.0066 ( 834 hom. )
Consequence
BHMT
NM_001713.3 synonymous
NM_001713.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.154
Genes affected
BHMT (HGNC:1047): (betaine--homocysteine S-methyltransferase) This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]
DMGDH (HGNC:24475): (dimethylglycine dehydrogenase) This gene encodes an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine to form sarcosine. The enzyme is found as a monomer in the mitochondrial matrix, and uses flavin adenine dinucleotide and folate as cofactors. Mutation in this gene causes dimethylglycine dehydrogenase deficiency, characterized by a fishlike body odor, chronic muscle fatigue, and elevated levels of the muscle form of creatine kinase in serum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP7
?
Synonymous conserved (PhyloP=-0.154 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BHMT | NM_001713.3 | c.792C>T | p.Leu264= | synonymous_variant | 6/8 | ENST00000274353.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BHMT | ENST00000274353.10 | c.792C>T | p.Leu264= | synonymous_variant | 6/8 | 1 | NM_001713.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0122 AC: 1859AN: 152182Hom.: 136 Cov.: 32
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GnomAD3 exomes AF: 0.0276 AC: 6934AN: 250838Hom.: 684 AF XY: 0.0214 AC XY: 2909AN XY: 135646
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GnomAD4 exome AF: 0.00658 AC: 9615AN: 1461208Hom.: 834 Cov.: 31 AF XY: 0.00571 AC XY: 4153AN XY: 726836
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GnomAD4 genome ? AF: 0.0122 AC: 1858AN: 152300Hom.: 135 Cov.: 32 AF XY: 0.0139 AC XY: 1036AN XY: 74468
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Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at