2-138005158-A-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_006895.3(HNMT):āc.456A>Gā(p.Pro152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,596,788 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 ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.000015 ( 0 hom. )
Consequence
HNMT
NM_006895.3 synonymous
NM_006895.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.315
Genes affected
HNMT (HGNC:5028): (histamine N-methyltransferase) In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase. This gene encodes the first enzyme which is found in the cytosol and uses S-adenosyl-L-methionine as the methyl donor. In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is not found in the central nervous system. A common genetic polymorphism affects the activity levels of this gene product in red blood cells. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 2-138005158-A-G is Benign according to our data. Variant chr2-138005158-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 750363.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.315 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNMT | NM_006895.3 | c.456A>G | p.Pro152= | synonymous_variant | 5/6 | ENST00000280097.5 | |
HNMT | XM_017003948.2 | c.354A>G | p.Pro118= | synonymous_variant | 5/6 | ||
HNMT | XM_011511064.3 | c.78A>G | p.Pro26= | synonymous_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNMT | ENST00000280097.5 | c.456A>G | p.Pro152= | synonymous_variant | 5/6 | 1 | NM_006895.3 | P1 | |
HNMT | ENST00000410115.5 | c.456A>G | p.Pro152= | synonymous_variant | 6/7 | 5 | P1 | ||
HNMT | ENST00000485653.1 | n.388A>G | non_coding_transcript_exon_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250442Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135326
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GnomAD4 exome AF: 0.0000145 AC: 21AN: 1444694Hom.: 0 Cov.: 27 AF XY: 0.0000111 AC XY: 8AN XY: 719788
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74294
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 11, 2018 | - - |
Computational scores
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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