rs769223
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000754.4(COMT):c.402G>A(p.Ala134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,612,960 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 (★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
COMT
NM_000754.4 synonymous
NM_000754.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.406
Genes affected
COMT (HGNC:2228): (catechol-O-methyltransferase) Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several transcript variants are formed through the use of alternative translation initiation sites and promoters. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 22-19963678-G-A is Benign according to our data. Variant chr22-19963678-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3239101.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.406 with no splicing effect.
BS2
?
High AC in GnomAd4 at 62 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COMT | NM_000754.4 | c.402G>A | p.Ala134= | synonymous_variant | 4/6 | ENST00000361682.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COMT | ENST00000361682.11 | c.402G>A | p.Ala134= | synonymous_variant | 4/6 | 1 | NM_000754.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000407 AC: 62AN: 152162Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000412 AC: 103AN: 249940Hom.: 0 AF XY: 0.000413 AC XY: 56AN XY: 135552
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GnomAD4 exome AF: 0.000199 AC: 290AN: 1460680Hom.: 0 Cov.: 30 AF XY: 0.000223 AC XY: 162AN XY: 726680
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GnomAD4 genome ? AF: 0.000407 AC: 62AN: 152280Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74462
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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 | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | COMT: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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