Variant 3-184036382-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145143.1(HTR3D):c.205C>A(p.Gln69Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HTR3D
NM_001145143.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0468733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3D	NM_001145143.1 linkuse as main transcript	c.205C>A	p.Gln69Lys	missense_variant	4/8	ENST00000428798.7	NP_001138615.1	Q70Z44-4
HTR3D	NM_001163646.2 linkuse as main transcript	c.388C>A	p.Gln130Lys	missense_variant	4/8		NP_001157118.1	Q70Z44-1
HTR3D	NM_182537.3 linkuse as main transcript	c.-18C>A		5_prime_UTR_variant	3/6		NP_872343.2	Q70Z44F6WC43
HTR3D	NM_001410851.1 linkuse as main transcript	c.3+1160C>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.205C>A	p.Gln69Lys	missense_variant	4/8	5	NM_001145143.1	ENSP00000405409.2	Q70Z44-4
HTR3D	ENST00000382489.3 linkuse as main transcript	c.388C>A	p.Gln130Lys	missense_variant	4/8	1		ENSP00000371929.3	Q70Z44-1
HTR3D	ENST00000334128.6 linkuse as main transcript	c.-18C>A		5_prime_UTR_variant	3/6	1		ENSP00000334315.2	F6WC43
HTR3D	ENST00000453435.1 linkuse as main transcript	c.3+1160C>A		intron_variant		1		ENSP00000389268.1	Q70Z44-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251334

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS 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:

0.00000137

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2021

The c.388C>A (p.Q130K) alteration is located in exon 4 (coding exon 4) of the HTR3D gene. This alteration results from a C to A substitution at nucleotide position 388, causing the glutamine (Q) at amino acid position 130 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.42

CADD

Benign

1.5

DANN

Benign

0.67

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.31

.;N

PROVEAN

Benign

0.37

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0090

.;B

Vest4

0.22

MutPred

0.46

.;Gain of ubiquitination at Q130 (P = 0.0117);

MVP

0.45

MPC

0.21

ClinPred

0.029

GERP RS

0.15

Varity_R

0.14

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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