3-184035998-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001163646.2(HTR3D):ā€‹c.278A>Gā€‹(p.His93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000774 in 1,550,452 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000064 ( 0 hom. )

Consequence

HTR3D
NM_001163646.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07012299).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HTR3DNM_001145143.1 linkuse as main transcriptc.112-17A>G intron_variant ENST00000428798.7 NP_001138615.1 Q70Z44-4
HTR3DNM_001163646.2 linkuse as main transcriptc.278A>G p.His93Arg missense_variant 3/8 NP_001157118.1 Q70Z44-1
HTR3DNM_182537.3 linkuse as main transcriptc.-31-371A>G intron_variant NP_872343.2 Q70Z44F6WC43
HTR3DNM_001410851.1 linkuse as main transcriptc.3+776A>G intron_variant NP_001397780.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HTR3DENST00000382489.3 linkuse as main transcriptc.278A>G p.His93Arg missense_variant 3/81 ENSP00000371929.3 Q70Z44-1
HTR3DENST00000428798.7 linkuse as main transcriptc.112-17A>G intron_variant 5 NM_001145143.1 ENSP00000405409.2 Q70Z44-4
HTR3DENST00000334128.6 linkuse as main transcriptc.-31-371A>G intron_variant 1 ENSP00000334315.2 F6WC43
HTR3DENST00000453435.1 linkuse as main transcriptc.3+776A>G intron_variant 1 ENSP00000389268.1 Q70Z44-3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000259
AC:
4
AN:
154694
Hom.:
0
AF XY:
0.0000244
AC XY:
2
AN XY:
82114
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000165
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.00000644
AC:
9
AN:
1398330
Hom.:
0
Cov.:
32
AF XY:
0.00000725
AC XY:
5
AN XY:
689718
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000113
Gnomad4 ASJ exome
AF:
0.0000796
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227

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 submitterclinical testingAmbry GeneticsNov 18, 2023The c.278A>G (p.H93R) alteration is located in exon 3 (coding exon 3) of the HTR3D gene. This alteration results from a A to G substitution at nucleotide position 278, causing the histidine (H) at amino acid position 93 to be replaced by an arginine (R). 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
0.086
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
13
DANN
Benign
0.73
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.0
N
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.13
Sift
Benign
0.37
T
Sift4G
Benign
0.25
T
Polyphen
0.012
B
Vest4
0.26
MutPred
0.37
Gain of MoRF binding (P = 0.0615);
MVP
0.63
MPC
0.21
ClinPred
0.048
T
GERP RS
3.1
Varity_R
0.17
gMVP
0.039

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs1426809912; hg19: chr3-183753786; COSMIC: COSV61915236; API