NM_001145143.1:c.329G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001145143.1(HTR3D):​c.329G>C​(p.Gly110Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,688 control chromosomes in the GnomAD database, including 169,278 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 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: 𝑓 0.50 (20231 hom., cov: 33)
  • Exomes 𝑓: 0.45 (149047 hom.)
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.131).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

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>C	p.Gly110Ala	missense	Exon 4 of 8	NP_001138615.1
	HTR3D	NM_182537.3		c.107G>C	p.Gly36Ala	missense	Exon 3 of 6	NP_872343.2
	HTR3D	NM_001163646.2		c.511+1G>C		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>C	p.Gly110Ala	missense	Exon 4 of 8	ENSP00000405409.2
	HTR3D	ENST00000334128.6	TSL:1	c.107G>C	p.Gly36Ala	missense	Exon 3 of 6	ENSP00000334315.2
	HTR3D	ENST00000382489.3	TSL:1	c.511+1G>C		splice_donor intron	N/A	ENSP00000371929.3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76288 AN: 152040 Hom.: 20212 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.517

GnomAD2 exomes AF: 0.456 AC: 114642 AN: 251224 AF XY: 0.452

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.496

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.448 AC: 654727 AN: 1461530 Hom.: 149047 Cov.: 59 AF XY: 0.448 AC XY: 325485 AN XY: 727062

African (AFR) AF: 0.678 AC: 22696 AN: 33474

American (AMR) AF: 0.437 AC: 19520 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 15079 AN: 26134

East Asian (EAS) AF: 0.553 AC: 21959 AN: 39698

South Asian (SAS) AF: 0.446 AC: 38446 AN: 86248

European-Finnish (FIN) AF: 0.328 AC: 17526 AN: 53406

Middle Eastern (MID) AF: 0.537 AC: 3086 AN: 5744

European-Non Finnish (NFE) AF: 0.439 AC: 488297 AN: 1111744

Other (OTH) AF: 0.466 AC: 28118 AN: 60384

GnomAD4 genome AF: 0.502 AC: 76347 AN: 152158 Hom.: 20231 Cov.: 33 AF XY: 0.495 AC XY: 36807 AN XY: 74390

African (AFR) AF: 0.665 AC: 27613 AN: 41518

American (AMR) AF: 0.465 AC: 7098 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2028 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2626 AN: 5176

South Asian (SAS) AF: 0.455 AC: 2197 AN: 4830

European-Finnish (FIN) AF: 0.309 AC: 3274 AN: 10582

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29933 AN: 68004

Other (OTH) AF: 0.510 AC: 1076 AN: 2108

Alfa AF: 0.427 Hom.: 4212

Bravo AF: 0.520

TwinsUK AF: 0.422 AC: 1563

ALSPAC AF: 0.441 AC: 1701

ESP6500AA AF: 0.646 AC: 2848

ESP6500EA AF: 0.449 AC: 3862

ExAC AF: 0.462 AC: 56051

Asia WGS AF: 0.484 AC: 1687 AN: 3478

EpiCase AF: 0.465

EpiControl AF: 0.470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.5
DANN	Benign	0.95
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.018	N
PhyloP100		0.66
ClinPred		0.0099	T
GERP RS		4.1
Mutation Taster		=23/77	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV61913608;