chr3-114147536-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000796.6(DRD3):c.405C>T(p.Pro135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,613,628 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 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
DRD3
NM_000796.6 synonymous
NM_000796.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.43
Genes affected
DRD3 (HGNC:3024): (dopamine receptor D3) This gene encodes the D3 subtype of the five (D1-D5) dopamine receptors. The activity of the D3 subtype receptor is mediated by G proteins which inhibit adenylyl cyclase. This receptor is localized to the limbic areas of the brain, which are associated with cognitive, emotional, and endocrine functions. Genetic variation in this gene may be associated with susceptibility to hereditary essential tremor 1. Alternative splicing of this gene results in transcript variants encoding different isoforms, although some variants may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 3-114147536-G-A is Benign according to our data. Variant chr3-114147536-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 748261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.43 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DRD3 | NM_000796.6 | c.405C>T | p.Pro135= | synonymous_variant | 4/7 | ENST00000383673.5 | |
DRD3 | NM_001282563.2 | c.405C>T | p.Pro135= | synonymous_variant | 5/8 | ||
DRD3 | NM_001290809.1 | c.405C>T | p.Pro135= | synonymous_variant | 5/8 | ||
DRD3 | NM_033663.6 | c.405C>T | p.Pro135= | synonymous_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DRD3 | ENST00000383673.5 | c.405C>T | p.Pro135= | synonymous_variant | 4/7 | 1 | NM_000796.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152094Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251290Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135778
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GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461534Hom.: 0 Cov.: 31 AF XY: 0.0000660 AC XY: 48AN XY: 726982
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152094Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74284
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | DRD3: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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