Variant 3-184104260-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001256613.2(HTR3E):c.358C>G(p.Leu120Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,613,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

HTR3E
NM_001256613.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.425

Variant links:

Genes affected

HTR3E (HGNC:24005): (5-hydroxytryptamine receptor 3E) This locus encodes a 5-hydroxytryptamine (serotonin) receptor subunit. The encoded protein, subunit E, may play a role in neurotransmission in myenteric neurons. Genes encoding subunits C, D and E form a cluster on chromosome 3. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2012]

HTR3E links:

HTR3E-AS1 (HGNC:):

HTR3E-AS1 links:

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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=0.1607365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3E	NM_001256613.2 linkuse as main transcript	c.358C>G	p.Leu120Val	missense_variant	4/9	ENST00000415389.6	NP_001243542.1	A5X5Y0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3E	ENST00000415389.6 linkuse as main transcript	c.358C>G	p.Leu120Val	missense_variant	4/9	1	NM_001256613.2	ENSP00000401444.2		A5X5Y0-1

Frequencies

GnomAD3 genomes

AF:

0.000257

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000272

AC:

AN:

250186

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000513

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000464

AC:

678

AN:

1460914

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

336

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000574

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000256

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000416

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

Jan 12, 2024

The c.403C>G (p.L135V) alteration is located in exon 3 (coding exon 3) of the HTR3E gene. This alteration results from a C to G substitution at nucleotide position 403, causing the leucine (L) at amino acid position 135 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.051

T;.;.;.;.;.

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.76

T;T;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.4

M;.;.;.;M;M

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Uncertain

0.29

Sift

Benign

0.20

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.96

D;P;P;.;P;.

Vest4

0.39

MVP

0.75

MPC

0.25

ClinPred

0.053

GERP RS

3.5

Varity_R

0.11

gMVP

0.026

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.

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