rs75040538

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001145143.1(HTR3D):ā€‹c.964C>Gā€‹(p.Leu322Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,613,584 control chromosomes in the GnomAD database, including 3,686 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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: š‘“ 0.057 ( 310 hom., cov: 32)
Exomes š‘“: 0.061 ( 3376 hom. )

Consequence

HTR3D
NM_001145143.1 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.455
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017104149).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HTR3DNM_001145143.1 linkuse as main transcriptc.964C>G p.Leu322Val missense_variant 7/8 ENST00000428798.7 NP_001138615.1 Q70Z44-4
HTR3DNM_001163646.2 linkuse as main transcriptc.1114C>G p.Leu372Val missense_variant 7/8 NP_001157118.1 Q70Z44-1
HTR3DNM_182537.3 linkuse as main transcriptc.589C>G p.Leu197Val missense_variant 5/6 NP_872343.2 Q70Z44F6WC43
HTR3DNM_001410851.1 linkuse as main transcriptc.451C>G p.Leu151Val missense_variant 4/5 NP_001397780.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HTR3DENST00000428798.7 linkuse as main transcriptc.964C>G p.Leu322Val missense_variant 7/85 NM_001145143.1 ENSP00000405409.2 Q70Z44-4
HTR3DENST00000382489.3 linkuse as main transcriptc.1114C>G p.Leu372Val missense_variant 7/81 ENSP00000371929.3 Q70Z44-1
HTR3DENST00000334128.6 linkuse as main transcriptc.589C>G p.Leu197Val missense_variant 5/61 ENSP00000334315.2 F6WC43
HTR3DENST00000453435.1 linkuse as main transcriptc.451C>G p.Leu151Val missense_variant 3/41 ENSP00000389268.1 Q70Z44-3

Frequencies

GnomAD3 genomes
AF:
0.0573
AC:
8717
AN:
152158
Hom.:
308
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0401
Gnomad AMI
AF:
0.0362
Gnomad AMR
AF:
0.0537
Gnomad ASJ
AF:
0.103
Gnomad EAS
AF:
0.164
Gnomad SAS
AF:
0.115
Gnomad FIN
AF:
0.0525
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0549
Gnomad OTH
AF:
0.0629
GnomAD3 exomes
AF:
0.0684
AC:
17038
AN:
249082
Hom.:
799
AF XY:
0.0708
AC XY:
9529
AN XY:
134684
show subpopulations
Gnomad AFR exome
AF:
0.0409
Gnomad AMR exome
AF:
0.0391
Gnomad ASJ exome
AF:
0.0947
Gnomad EAS exome
AF:
0.162
Gnomad SAS exome
AF:
0.111
Gnomad FIN exome
AF:
0.0478
Gnomad NFE exome
AF:
0.0559
Gnomad OTH exome
AF:
0.0694
GnomAD4 exome
AF:
0.0612
AC:
89482
AN:
1461308
Hom.:
3376
Cov.:
88
AF XY:
0.0623
AC XY:
45259
AN XY:
726906
show subpopulations
Gnomad4 AFR exome
AF:
0.0375
Gnomad4 AMR exome
AF:
0.0412
Gnomad4 ASJ exome
AF:
0.0937
Gnomad4 EAS exome
AF:
0.195
Gnomad4 SAS exome
AF:
0.106
Gnomad4 FIN exome
AF:
0.0484
Gnomad4 NFE exome
AF:
0.0540
Gnomad4 OTH exome
AF:
0.0689
GnomAD4 genome
AF:
0.0573
AC:
8722
AN:
152276
Hom.:
310
Cov.:
32
AF XY:
0.0578
AC XY:
4305
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.0402
Gnomad4 AMR
AF:
0.0536
Gnomad4 ASJ
AF:
0.103
Gnomad4 EAS
AF:
0.164
Gnomad4 SAS
AF:
0.115
Gnomad4 FIN
AF:
0.0525
Gnomad4 NFE
AF:
0.0549
Gnomad4 OTH
AF:
0.0622
Alfa
AF:
0.0585
Hom.:
96
Bravo
AF:
0.0559
TwinsUK
AF:
0.0480
AC:
178
ALSPAC
AF:
0.0464
AC:
179
ESP6500AA
AF:
0.0438
AC:
193
ESP6500EA
AF:
0.0592
AC:
509
ExAC
AF:
0.0687
AC:
8342
Asia WGS
AF:
0.133
AC:
463
AN:
3478
EpiCase
AF:
0.0597
EpiControl
AF:
0.0650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
13
DANN
Benign
0.96
DEOGEN2
Benign
0.0022
.;.;T;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.081
N
LIST_S2
Uncertain
0.88
D;D;D;D
MetaRNN
Benign
0.0017
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.5
.;.;M;.
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.21
T;T;T;T
Sift4G
Benign
0.43
T;T;T;T
Polyphen
0.94
P;.;D;P
Vest4
0.13
MPC
0.67
ClinPred
0.0099
T
GERP RS
1.8
Varity_R
0.063
gMVP
0.053

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: rs75040538; hg19: chr3-183756391; COSMIC: COSV61914742; API