Genetic Variant HTR3D:p.Pro105Ser (chr3-184036490-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 NM_001145143.1(HTR3D):c.313C>T(p.Pro105Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

HTR3D
NM_001145143.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.04

Publications

10 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:

Genome browser will be placed here

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=0.22851345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HTR3D	NM_001145143.1 link	c.313C>T	p.Pro105Ser	missense_variant	Exon 4 of 8	ENST00000428798.7	NP_001138615.1
HTR3D	NM_001163646.2 link	c.496C>T	p.Pro166Ser	missense_variant	Exon 4 of 8		NP_001157118.1
HTR3D	NM_182537.3 link	c.91C>T	p.Pro31Ser	missense_variant	Exon 3 of 6		NP_872343.2
HTR3D	NM_001410851.1 link	c.3+1268C>T		intron_variant	Intron 2 of 4		NP_001397780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
HTR3D	ENST00000428798.7 link	c.313C>T	p.Pro105Ser	missense_variant	Exon 4 of 8	5	NM_001145143.1	ENSP00000405409.2
HTR3D	ENST00000382489.3 link	c.496C>T	p.Pro166Ser	missense_variant	Exon 4 of 8	1		ENSP00000371929.3
HTR3D	ENST00000334128.6 link	c.91C>T	p.Pro31Ser	missense_variant	Exon 3 of 6	1		ENSP00000334315.2
HTR3D	ENST00000453435.1 link	c.3+1268C>T		intron_variant	Intron 1 of 3	1		ENSP00000389268.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251358

AF XY:

0.00000736

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000629

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0015

.;.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

0.90

.;.;L

PhyloP100

7.0

PROVEAN

Benign

-0.68

N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.18

T;T;T

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

0.99

D;.;B

Vest4

0.27

MutPred

0.34

.;.;Gain of sheet (P = 0.039);

MVP

0.63

MPC

0.16

ClinPred

0.28

GERP RS

5.0

Varity_R

0.057

gMVP

0.037

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over