Variant 3-184104812-G-A 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.415G>A(p.Gly139Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

HTR3E
NM_001256613.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242

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=0.11900875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3E	NM_001256613.2 linkuse as main transcript	c.415G>A	p.Gly139Ser	missense_variant	5/9	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.415G>A	p.Gly139Ser	missense_variant	5/9	1	NM_001256613.2	ENSP00000401444.2		A5X5Y0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727082

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

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

May 13, 2024

The c.460G>A (p.G154S) alteration is located in exon 4 (coding exon 4) of the HTR3E gene. This alteration results from a G to A substitution at nucleotide position 460, causing the glycine (G) at amino acid position 154 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.033

T;.;.;.;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.71

T;T;T;T;T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.1

L;.;.;.;L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.075

T;T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T;T

Polyphen

0.063

B;B;B;.;B;.

Vest4

0.078

MutPred

0.29

Gain of glycosylation at T136 (P = 0.0195);.;.;.;Gain of glycosylation at T136 (P = 0.0195);.;

MVP

0.64

MPC

0.064

ClinPred

0.18

GERP RS

3.8

Varity_R

0.070

gMVP

0.096

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over