dbSNP rs7627615: HTR3E:p.Ala71Thr (chr3-184100628-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256613.2(HTR3E):c.211G>A(p.Ala71Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,613,590 control chromosomes in the GnomAD database, including 308,536 homozygotes. 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 Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.68 ( 36625 hom., cov: 30)

Exomes 𝑓: 0.61 ( 271911 hom. )

Consequence

HTR3E
NM_001256613.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.49

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:41032): (HTR3E antisense RNA 1)

HTR3E-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.6547994E-7).

BP6

Variant 3-184100628-G-A is Benign according to our data. Variant chr3-184100628-G-A is described in ClinVar as [Benign]. Clinvar id is 1242214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3E	NM_001256613.2 link	c.211G>A	p.Ala71Thr	missense_variant	Exon 2 of 9	ENST00000415389.6	NP_001243542.1	A5X5Y0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3E	ENST00000415389.6 link	c.211G>A	p.Ala71Thr	missense_variant	Exon 2 of 9	1	NM_001256613.2	ENSP00000401444.2		A5X5Y0-1

Frequencies

GnomAD3 genomes

AF:

0.682

AC:

103533

AN:

151720

Hom.:

36580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.878

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.604

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.640

AC:

160765

AN:

251206

Hom.:

52593

AF XY:

0.631

AC XY:

85671

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.715

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.768

Gnomad SAS exome

AF:

0.612

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.591

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.606

AC:

886498

AN:

1461752

Hom.:

271911

Cov.:

AF XY:

0.605

AC XY:

439852

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.892

Gnomad4 AMR exome

AF:

0.707

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.758

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.632

GnomAD4 genome

AF:

0.683

AC:

103632

AN:

151838

Hom.:

36625

Cov.:

AF XY:

0.680

AC XY:

50404

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.878

Gnomad4 AMR

AF:

0.674

Gnomad4 ASJ

AF:

0.604

Gnomad4 EAS

AF:

0.763

Gnomad4 SAS

AF:

0.614

Gnomad4 FIN

AF:

0.537

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.680

Alfa

AF:

0.614

Hom.:

74944

Bravo

AF:

0.706

TwinsUK

AF:

0.592

AC:

2196

ALSPAC

AF:

0.606

AC:

2337

ESP6500AA

AF:

0.871

AC:

3837

ESP6500EA

AF:

0.588

AC:

5058

ExAC

AF:

0.640

AC:

77751

Asia WGS

AF:

0.732

AC:

2545

AN:

3478

EpiCase

AF:

0.603

EpiControl

AF:

0.610

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23928294) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

DANN

Benign

0.87

DEOGEN2

Benign

0.042

T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.046

T;T;T;T;T

MetaRNN

Benign

6.7e-7

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.2

N;N;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

2.9

N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.061

MPC

0.055

ClinPred

0.0027

GERP RS

2.6

Varity_R

0.023

gMVP

0.030

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