rs6443930

Positions:

• chr3-184036506-G-A
• chr3-184036506-G-C
• chr3-184036506-G-T

Variant summary

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

The ENST00000382489.3(HTR3D):​c.511+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HTR3D ENST00000382489.3 splice_donor
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

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

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/exons	MANE	UniProt
HTR3D	NM_001145143.1	c.329G>A	p.Gly110Asp	missense_variant	4/8	ENST00000428798.7
HTR3D	NM_001163646.2	c.511+1G>A		splice_donor_variant
HTR3D	NM_182537.3	c.107G>A	p.Gly36Asp	missense_variant	3/6
HTR3D	NM_001410851.1	c.3+1284G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3D	ENST00000382489.3	c.511+1G>A		splice_donor_variant		1		P1
HTR3D	ENST00000428798.7	c.329G>A	p.Gly110Asp	missense_variant	4/8	5	NM_001145143.1
HTR3D	ENST00000334128.6	c.107G>A	p.Gly36Asp	missense_variant	3/6	1
HTR3D	ENST00000453435.1	c.3+1284G>A		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	P;P;P;P
ClinPred		0.23	T
GERP RS		4.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs6443930; hg19: chr3-183754294;