chr9-133636433-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000787.4(DBH):c.62T>C(p.Met21Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M21R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000787.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DBH | NM_000787.4 | c.62T>C | p.Met21Thr | missense_variant | 1/12 | ENST00000393056.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DBH | ENST00000393056.8 | c.62T>C | p.Met21Thr | missense_variant | 1/12 | 1 | NM_000787.4 | P1 | |
DBH | ENST00000263611.3 | c.56T>C | p.Met19Thr | missense_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250200Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135518
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460578Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 726578
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Orthostatic hypotension 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with DBH-related conditions. This variant is present in population databases (rs770621845, ExAC 0.003%). This sequence change replaces methionine with threonine at codon 21 of the DBH protein (p.Met21Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at