chr3-184036506-G-A

Variant names:

• chr3-184036506-G-A
• rs6443930
• NM_001145143.1:c.329G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145143.1(HTR3D):​c.329G>A​(p.Gly110Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/14 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)
• Consequence: HTR3D NM_001145143.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 45 publications found

Genes affected

HTR3D (HGNC:24004): (5-hydroxytryptamine receptor 3D) The protein encoded this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit D of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a mitogen and a hormone. This hormone has been linked to neuropsychiatric disorders, including anxiety, depression, and migraine. Serotonin receptors causes fast and depolarizing responses in neurons following activation. The genes encoding subunits C, D and E of this type 3 receptor form a cluster on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.1).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145143.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3D	NM_001145143.1	MANE Select	c.329G>A	p.Gly110Asp	missense	Exon 4 of 8	NP_001138615.1
	HTR3D	NM_182537.3		c.107G>A	p.Gly36Asp	missense	Exon 3 of 6	NP_872343.2
	HTR3D	NM_001163646.2		c.511+1G>A		splice_donor intron	N/A	NP_001157118.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3D	ENST00000428798.7	TSL:5 MANE Select	c.329G>A	p.Gly110Asp	missense	Exon 4 of 8	ENSP00000405409.2
	HTR3D	ENST00000334128.6	TSL:1	c.107G>A	p.Gly36Asp	missense	Exon 3 of 6	ENSP00000334315.2
	HTR3D	ENST00000382489.3	TSL:1	c.511+1G>A		splice_donor intron	N/A	ENSP00000371929.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.97
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.024	T
PhyloP100		0.66
ClinPred		0.23	T
GERP RS		4.1
Mutation Taster		=23/77	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6443930; hg19: chr3-183754294;