3-114147537-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000796.6(DRD3):c.404C>A(p.Pro135His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P135P) has been classified as Likely benign.
Frequency
Consequence
NM_000796.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DRD3 | NM_000796.6 | c.404C>A | p.Pro135His | missense_variant | 4/7 | ENST00000383673.5 | |
DRD3 | NM_001282563.2 | c.404C>A | p.Pro135His | missense_variant | 5/8 | ||
DRD3 | NM_001290809.1 | c.404C>A | p.Pro135His | missense_variant | 5/8 | ||
DRD3 | NM_033663.6 | c.404C>A | p.Pro135His | missense_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DRD3 | ENST00000383673.5 | c.404C>A | p.Pro135His | missense_variant | 4/7 | 1 | NM_000796.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251320Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135792
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461550Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726996
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Tremor, hereditary essential, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Breda Genetics srl | Jul 01, 2022 | Based on allele frequency, in-silico prediction scores and a certain overlap with the clinical phenotype, we interpreted this variant at least as of uncertain significance. The lack of one or more of the following features has discouraged further investigations: lack of a possible second hit in autosomal recessive conditions, presence of healthy controls in databases for autosomal dominant conditions, presence of unmatching cardinal clinical features in the patient or in the known gene-disease association, and/or variant type outside the known gene mutational spectrum - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at