3-184036093-G-C

Variant names:

• chr3-184036093-G-C
• rs1176957558
• NM_001145143.1:c.190G>C

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.190G>C​(p.Glu64Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E64K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: HTR3D NM_001145143.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 0 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 (MetaRNN=0.08664894).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3D	NM_001145143.1	MANE Select	c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	NP_001138615.1	Q70Z44-4
	HTR3D	NM_001163646.2		c.373G>C	p.Glu125Gln	missense	Exon 3 of 8	NP_001157118.1	Q70Z44-1
	HTR3D	NM_182537.3		c.-31-276G>C		intron	N/A	NP_872343.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3D	ENST00000428798.7	TSL:5 MANE Select	c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	ENSP00000405409.2	Q70Z44-4
	HTR3D	ENST00000382489.3	TSL:1	c.373G>C	p.Glu125Gln	missense	Exon 3 of 8	ENSP00000371929.3	Q70Z44-1
	HTR3D	ENST00000334128.6	TSL:1	c.-31-276G>C		intron	N/A	ENSP00000334315.2	F6WC43

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398316 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689684

African (AFR) AF: 0.00 AC: 0 AN: 31528

American (AMR) AF: 0.00 AC: 0 AN: 35374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25112

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078620

Other (OTH) AF: 0.00 AC: 0 AN: 57950

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.084
DANN	Benign	0.61
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.76
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.16
Sift	Benign	0.44	T
Sift4G	Uncertain	0.027	D
Polyphen		0.52	P
Vest4		0.30
MutPred		0.24		Loss of sheet (P = 0.1907)
MVP		0.31
MPC		0.29
ClinPred		0.17	T
GERP RS		-4.7
Varity_R		0.14
gMVP		0.11
Mutation Taster		=98/2	polymorphism

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: rs1176957558; hg19: chr3-183753881;