NM_001145143.1:c.313C>G

Variant names:

• chr3-184036490-C-G
• rs73183412
• NM_001145143.1:c.313C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145143.1(HTR3D):​c.313C>G​(p.Pro105Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0649 in 1,613,946 control chromosomes in the GnomAD database, including 3,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.064 (346 hom., cov: 33)
  • Exomes 𝑓: 0.065 (3477 hom.)
• Consequence: HTR3D NM_001145143.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001760155).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 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.313C>G	p.Pro105Ala	missense	Exon 4 of 8	NP_001138615.1
	HTR3D	NM_001163646.2		c.496C>G	p.Pro166Ala	missense	Exon 4 of 8	NP_001157118.1
	HTR3D	NM_182537.3		c.91C>G	p.Pro31Ala	missense	Exon 3 of 6	NP_872343.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3D	ENST00000428798.7	TSL:5 MANE Select	c.313C>G	p.Pro105Ala	missense	Exon 4 of 8	ENSP00000405409.2
	HTR3D	ENST00000382489.3	TSL:1	c.496C>G	p.Pro166Ala	missense	Exon 4 of 8	ENSP00000371929.3
	HTR3D	ENST00000334128.6	TSL:1	c.91C>G	p.Pro31Ala	missense	Exon 3 of 6	ENSP00000334315.2

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9718 AN: 152160 Hom.: 347 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0753

GnomAD2 exomes AF: 0.0732 AC: 18387 AN: 251358 AF XY: 0.0701

Gnomad AFR exome AF: 0.0481

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.0543

Gnomad FIN exome AF: 0.0392

Gnomad NFE exome AF: 0.0654

Gnomad OTH exome AF: 0.0826

GnomAD4 exome AF: 0.0650 AC: 95030 AN: 1461668 Hom.: 3477 Cov.: 33 AF XY: 0.0645 AC XY: 46909 AN XY: 727128

African (AFR) AF: 0.0514 AC: 1719 AN: 33476

American (AMR) AF: 0.135 AC: 6036 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4324 AN: 26134

East Asian (EAS) AF: 0.0610 AC: 2423 AN: 39698

South Asian (SAS) AF: 0.0478 AC: 4123 AN: 86252

European-Finnish (FIN) AF: 0.0418 AC: 2234 AN: 53418

Middle Eastern (MID) AF: 0.0958 AC: 552 AN: 5760

European-Non Finnish (NFE) AF: 0.0624 AC: 69346 AN: 1111854

Other (OTH) AF: 0.0708 AC: 4273 AN: 60384

GnomAD4 genome AF: 0.0638 AC: 9712 AN: 152278 Hom.: 346 Cov.: 33 AF XY: 0.0633 AC XY: 4715 AN XY: 74458

African (AFR) AF: 0.0498 AC: 2071 AN: 41558

American (AMR) AF: 0.107 AC: 1631 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3472

East Asian (EAS) AF: 0.0577 AC: 299 AN: 5180

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4824

European-Finnish (FIN) AF: 0.0347 AC: 368 AN: 10620

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4299 AN: 68018

Other (OTH) AF: 0.0740 AC: 156 AN: 2108

Alfa AF: 0.0707 Hom.: 288

Bravo AF: 0.0709

TwinsUK AF: 0.0623 AC: 231

ALSPAC AF: 0.0677 AC: 261

ESP6500AA AF: 0.0449 AC: 198

ESP6500EA AF: 0.0673 AC: 579

ExAC AF: 0.0705 AC: 8558

Asia WGS AF: 0.0450 AC: 159 AN: 3478

EpiCase AF: 0.0727

EpiControl AF: 0.0687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.47
DEOGEN2	Benign	0.0022	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.90	L
PhyloP100		7.0
PROVEAN	Benign	-0.37	N
REVEL	Uncertain	0.30
Sift	Benign	0.32	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.23
MPC		0.16
ClinPred		0.026	T
GERP RS		5.0
Varity_R		0.061
gMVP		0.023
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73183412; hg19: chr3-183754278; COSMIC: COSV61914206;