3-184036084-G-A

Position:

chr3-184036084-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145143.1(HTR3D):c.181G>A(p.Val61Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,551,436 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

HTR3D
NM_001145143.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.877

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0074207485).

BP6

Variant 3-184036084-G-A is Benign according to our data. Variant chr3-184036084-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3107554.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3D	NM_001145143.1 linkuse as main transcript	c.181G>A	p.Val61Ile	missense_variant	3/8	ENST00000428798.7	NP_001138615.1	Q70Z44-4
HTR3D	NM_001163646.2 linkuse as main transcript	c.364G>A	p.Val122Ile	missense_variant	3/8		NP_001157118.1	Q70Z44-1
HTR3D	NM_182537.3 linkuse as main transcript	c.-31-285G>A		intron_variant			NP_872343.2	Q70Z44F6WC43
HTR3D	NM_001410851.1 linkuse as main transcript	c.3+862G>A		intron_variant			NP_001397780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HTR3D	ENST00000428798.7 linkuse as main transcript	c.181G>A	p.Val61Ile	missense_variant	3/8	5	NM_001145143.1	ENSP00000405409.2	Q70Z44-4
HTR3D	ENST00000382489.3 linkuse as main transcript	c.364G>A	p.Val122Ile	missense_variant	3/8	1		ENSP00000371929.3	Q70Z44-1
HTR3D	ENST00000334128.6 linkuse as main transcript	c.-31-285G>A		intron_variant		1		ENSP00000334315.2	F6WC43
HTR3D	ENST00000453435.1 linkuse as main transcript	c.3+862G>A		intron_variant		1		ENSP00000389268.1	Q70Z44-3

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

148

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000824

AC:

129

AN:

156468

Hom.:

AF XY:

0.000785

AC XY:

AN XY:

82854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000693

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000237

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

AF:

0.00149

AC:

2078

AN:

1399134

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1008

AN XY:

690100

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.000674

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.000406

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000972

AC:

148

AN:

152302

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00176

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.000888

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00189

AC:

ExAC

AF:

0.000325

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.83

DANN

Benign

0.22

DEOGEN2

Benign

0.040

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

.;N

PROVEAN

Benign

0.66

N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.015

.;B

Vest4

0.15

MVP

0.20

MPC

0.13

ClinPred

0.035

GERP RS

-1.2

Varity_R

0.023

gMVP

0.019

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over