rs745685569
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000787.4(DBH):āc.146A>Gā(p.Tyr49Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y49F) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DBH | NM_000787.4 | c.146A>G | p.Tyr49Cys | missense_variant | 1/12 | ENST00000393056.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DBH | ENST00000393056.8 | c.146A>G | p.Tyr49Cys | missense_variant | 1/12 | 1 | NM_000787.4 | P1 | |
DBH | ENST00000263611.3 | c.140A>G | p.Tyr47Cys | missense_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249856Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135350
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461152Hom.: 1 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 726922
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Orthostatic hypotension 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | 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. This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 49 of the DBH protein (p.Tyr49Cys). This variant is present in population databases (rs745685569, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DBH-related conditions. ClinVar contains an entry for this variant (Variation ID: 565924). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DBH protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at