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GeneBe

rs6280

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000796(DRD3):c.25G>A(p.Gly9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151970 control chromosomes in the gnomAD Genomes database, including 25266 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (β˜…β˜…).

Frequency

Genomes: 𝑓 0.55 ( 25266 hom., cov: 32)
Exomes 𝑓: 0.63 ( 30801 hom. )

Consequence

DRD3
NM_000796 missense

Scores

15

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2O:2

Conservation

PhyloP100: -0.471

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=2.230764E-6).
BP6
?
Variant 3:114171968-C>T is Benign according to our data. Variant chr3-114171968-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 16770. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DRD3NM_000796.6 linkuse as main transcriptc.25G>A p.Gly9Ser missense_variant 2/7 ENST00000383673.5
DRD3NM_001282563.2 linkuse as main transcriptc.25G>A p.Gly9Ser missense_variant 3/8
DRD3NM_001290809.1 linkuse as main transcriptc.25G>A p.Gly9Ser missense_variant 3/8
DRD3NM_033663.6 linkuse as main transcriptc.25G>A p.Gly9Ser missense_variant 2/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DRD3ENST00000383673.5 linkuse as main transcriptc.25G>A p.Gly9Ser missense_variant 2/71 NM_000796.6 P1P35462-1

Frequencies

GnomAD3 genomes
AF:
0.547
AC:
83156
AN:
151970
Hom.:
25266
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.269
Gnomad AMI
AF:
0.648
Gnomad AMR
AF:
0.547
Gnomad ASJ
AF:
0.707
Gnomad EAS
AF:
0.698
Gnomad SAS
AF:
0.590
Gnomad FIN
AF:
0.662
Gnomad MID
AF:
0.601
Gnomad NFE
AF:
0.673
Gnomad OTH
AF:
0.588
GnomAD3 exomes
AF:
0.628
AC:
95572
AN:
152300
Hom.:
30801
AF XY:
0.634
AC XY:
51824
AN XY:
81692
show subpopulations
Gnomad AFR exome
AF:
0.263
Gnomad AMR exome
AF:
0.549
Gnomad ASJ exome
AF:
0.726
Gnomad EAS exome
AF:
0.696
Gnomad SAS exome
AF:
0.592
Gnomad FIN exome
AF:
0.674
Gnomad NFE exome
AF:
0.680
Gnomad OTH exome
AF:
0.662
GnomAD4 exome
AF:
0.653
AC:
877824
AN:
1344156
Hom.:
290755
AF XY:
0.653
AC XY:
429752
AN XY:
658204
show subpopulations
Gnomad4 AFR exome
AF:
0.245
Gnomad4 AMR exome
AF:
0.547
Gnomad4 ASJ exome
AF:
0.714
Gnomad4 EAS exome
AF:
0.714
Gnomad4 SAS exome
AF:
0.586
Gnomad4 FIN exome
AF:
0.675
Gnomad4 NFE exome
AF:
0.669
Gnomad4 OTH exome
AF:
0.630
Alfa
AF:
0.651
Hom.:
80419
Bravo
AF:
0.528
TwinsUK
AF:
0.662
AC:
2454
ALSPAC
AF:
0.662
AC:
2551
ESP6500AA
AF:
0.276
AC:
1216
ESP6500EA
AF:
0.666
AC:
5723
ExAC
AF:
0.585
AC:
70275
Asia WGS
AF:
0.615
AC:
2140
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 09, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Tremor, hereditary essential, 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Schizophrenia, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 06, 2007- -
Essential tremor, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMar 06, 2007- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.70
T
BayesDel_noAF
Benign
-0.63
Cadd
Benign
0.048
Dann
Benign
0.82
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0036
N
MetaRNN
Benign
0.0000022
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.98
N;N;N;N
REVEL
Benign
0.033
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
.;.;B;.
Vest4
0.022
MPC
0.37
ClinPred
0.00050
T
GERP RS
-1.5
gMVP
0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6280; hg19: chr3-113890815; COSMIC: COSV55678322;