Genetic Variant HTR3D:p.Pro91Ser (chr3-184035991-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000382489.3(HTR3D):c.271C>T(p.Pro91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,770 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. P91A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HTR3D
ENST00000382489.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.619

Publications

0 publications found

Variant links:

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]

HTR3D links:

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ACMG classification

Classification was made for transcript

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=0.0798257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3D	NM_001145143.1 link	c.112-24C>T		intron_variant	Intron 2 of 7	ENST00000428798.7	NP_001138615.1	Q70Z44-4
HTR3D	NM_001163646.2 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 3 of 8		NP_001157118.1	Q70Z44-1
HTR3D	NM_182537.3 link	c.-31-378C>T		intron_variant	Intron 2 of 5		NP_872343.2	Q70Z44F6WC43
HTR3D	NM_001410851.1 link	c.3+769C>T		intron_variant	Intron 2 of 4		NP_001397780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTR3D	ENST00000382489.3 link	c.271C>T	p.Pro91Ser	missense_variant	Exon 3 of 8	1		ENSP00000371929.3	Q70Z44-1
HTR3D	ENST00000428798.7 link	c.112-24C>T		intron_variant	Intron 2 of 7	5	NM_001145143.1	ENSP00000405409.2	Q70Z44-4
HTR3D	ENST00000334128.6 link	c.-31-378C>T		intron_variant	Intron 2 of 5	1		ENSP00000334315.2	F6WC43
HTR3D	ENST00000453435.1 link	c.3+769C>T		intron_variant	Intron 1 of 3	1		ENSP00000389268.1	Q70Z44-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000650

AC:

AN:

153868

AF XY:

0.0000122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397770

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31510

American (AMR)

AF:

0.00

AC:

AN:

35258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25098

East Asian (EAS)

AF:

0.00

AC:

AN:

35728

South Asian (SAS)

AF:

0.0000253

AC:

AN:

78904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078460

Other (OTH)

AF:

0.0000173

AC:

AN:

57910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.68

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.015

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.31

M_CAP

Benign

0.0082

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

PhyloP100

-0.62

PROVEAN

Benign

0.81

REVEL

Benign

0.13

Sift

Benign

0.42

Sift4G

Benign

0.74

Polyphen

0.012

Vest4

0.23

MutPred

0.24

Gain of sheet (P = 0.0827);

MVP

0.24

MPC

0.16

ClinPred

0.036

GERP RS

-2.8

Varity_R

0.030

gMVP

0.061

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over