11-637426-G-C

Variant names:

• chr11-637426-G-C
• NM_000797.4:c.122G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000797.4(DRD4):​c.122G>C​(p.Gly41Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,374,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: DRD4 NM_000797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973

Genes affected

DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRD4	NM_000797.4	c.122G>C	p.Gly41Ala	missense_variant	Exon 1 of 4	ENST00000176183.6	NP_000788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRD4	ENST00000176183.6	c.122G>C	p.Gly41Ala	missense_variant	Exon 1 of 4	1	NM_000797.4	ENSP00000176183.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1374898 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 677800

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000285

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.91
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.67	T
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.23
Sift	Benign	0.57	T
Sift4G	Benign	0.13	T
Vest4		0.39
MutPred		0.42		Loss of disorder (P = 0.2747);
MVP		0.69
MPC		0.31
ClinPred		0.89	D
GERP RS		2.4
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-637426;