Genetic Variant NM_000794.5:c.1324G>A (chr5-175441776-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000794.5(DRD1):c.1324G>A(p.Gly442Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,430,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

DRD1
NM_000794.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

Publications

0 publications found

Variant links:

Genes affected

DRD1 (HGNC:3020): (dopamine receptor D1) This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein coupled receptor stimulates adenylyl cyclase and activates cyclic AMP-dependent protein kinases. D1 receptors regulate neuronal growth and development, mediate some behavioral responses, and modulate dopamine receptor D2-mediated events. Alternate transcription initiation sites result in two transcript variants of this gene. [provided by RefSeq, Jul 2008]

DRD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000794.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD1	NM_000794.5	MANE Select	c.1324G>A	p.Gly442Ser	missense	Exon 2 of 2	NP_000785.1	P21728

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRD1	ENST00000393752.3	TSL:2 MANE Select	c.1324G>A	p.Gly442Ser	missense	Exon 2 of 2	ENSP00000377353.1	P21728
DRD1	ENST00000950668.1		c.1324G>A	p.Gly442Ser	missense	Exon 3 of 3	ENSP00000620727.1
DRD1	ENST00000950669.1		c.1324G>A	p.Gly442Ser	missense	Exon 2 of 2	ENSP00000620728.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000909

AC:

AN:

1430892

Hom.:

Cov.:

AF XY:

0.00000990

AC XY:

AN XY:

707290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32600

American (AMR)

AF:

0.00

AC:

AN:

41706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24338

East Asian (EAS)

AF:

0.00

AC:

AN:

39288

South Asian (SAS)

AF:

0.00

AC:

AN:

81522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.0000110

AC:

AN:

1094758

Other (OTH)

AF:

0.0000170

AC:

AN:

58898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.59

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.0

PhyloP100

7.8

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

REVEL

Benign

0.26

Sift

Benign

0.035

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.61

MutPred

0.33

Gain of disorder (P = 0.0447)

MVP

0.76

MPC

1.5

ClinPred

0.97

GERP RS

5.4

Varity_R

0.17

gMVP

0.69

Mutation Taster

=23/77

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over