chr3-184032967-C-A

Variant names:

• chr3-184032967-C-A
• rs910167662
• ENST00000382489.3:c.137C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163646.2(HTR3D):​c.137C>A​(p.Ala46Glu) 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. 14/20 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. A46V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR3D NM_001163646.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13388374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3D	NM_001145143.1	c.66+1160C>A		intron_variant	Intron 1 of 7	ENST00000428798.7	NP_001138615.1
HTR3D	NM_001163646.2	c.137C>A	p.Ala46Glu	missense_variant	Exon 1 of 8		NP_001157118.1
HTR3D	NM_182537.3	c.-198+1396C>A		intron_variant	Intron 1 of 5		NP_872343.2
HTR3D	NM_001410851.1	c.-164+1396C>A		intron_variant	Intron 1 of 4		NP_001397780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3D	ENST00000382489.3	c.137C>A	p.Ala46Glu	missense_variant	Exon 1 of 8	1		ENSP00000371929.3
HTR3D	ENST00000428798.7	c.66+1160C>A		intron_variant	Intron 1 of 7	5	NM_001145143.1	ENSP00000405409.2
HTR3D	ENST00000334128.6	c.-198+1396C>A		intron_variant	Intron 1 of 5	1		ENSP00000334315.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.2	L
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.47	P
Vest4		0.21
MutPred		0.42		Gain of ubiquitination at K51 (P = 0.0444);
MVP		0.55
MPC		0.41
ClinPred		0.70	D
GERP RS		2.1
Varity_R		0.14
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs910167662; hg19: chr3-183750755;