11-637383-T-C

Position:

• chr11-637383-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000797.4(DRD4):​c.79T>C​(p.Ser27Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,203,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: DRD4 NM_000797.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.206

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07008657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRD4	NM_000797.4	c.79T>C	p.Ser27Pro	missense_variant	1/4	ENST00000176183.6	NP_000788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRD4	ENST00000176183.6	c.79T>C	p.Ser27Pro	missense_variant	1/4	1	NM_000797.4	ENSP00000176183	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1203142 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 588032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000205

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.79T>C (p.S27P) alteration is located in exon 1 (coding exon 1) of the DRD4 gene. This alteration results from a T to C substitution at nucleotide position 79, causing the serine (S) at amino acid position 27 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.6
DANN	Benign	0.41
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0028	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.20	N
REVEL	Benign	0.059
Sift	Benign	0.33	T
Sift4G	Benign	0.39	T
Vest4		0.16
MutPred		0.16		Loss of phosphorylation at S27 (P = 0.029);
MVP		0.29
MPC		0.36
ClinPred		0.73	D
GERP RS		-1.6
gMVP		0.33

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: chr11-637383;