Variant 3-184105280-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001256613.2(HTR3E):c.573G>C(p.Leu191Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,206 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: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HTR3E
NM_001256613.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.202

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28297615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3E	NM_001256613.2 linkuse as main transcript	c.573G>C	p.Leu191Phe	missense_variant	6/9	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.573G>C	p.Leu191Phe	missense_variant	6/9	1	NM_001256613.2	ENSP00000401444.2		A5X5Y0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249422

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000997

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460206

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Feb 10, 2022

The c.618G>C (p.L206F) alteration is located in exon 5 (coding exon 5) of the HTR3E gene. This alteration results from a G to C substitution at nucleotide position 618, causing the leucine (L) at amino acid position 206 to be replaced by a phenylalanine (F). 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

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

T;.;.;.;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.069

LIST_S2

Uncertain

0.86

D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.28

T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.6

M;.;.;.;M;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Uncertain

0.43

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Uncertain

0.052

T;T;T;T;T;T

Polyphen

0.96

D;P;D;.;D;.

Vest4

0.38

MutPred

0.44

Gain of glycosylation at T186 (P = 0.0581);.;.;.;Gain of glycosylation at T186 (P = 0.0581);.;

MVP

0.75

MPC

0.29

ClinPred

0.61

GERP RS

-1.0

Varity_R

0.049

gMVP

0.027

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