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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

53 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.640

AC:

160765

AN:

251206

AF XY:

0.631

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 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

African (AFR)

AF:

0.892

AC:

29872

AN:

33480

American (AMR)

AF:

0.707

AC:

31621

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

16075

AN:

26136

East Asian (EAS)

AF:

0.758

AC:

30104

AN:

39696

South Asian (SAS)

AF:

0.606

AC:

52277

AN:

86252

European-Finnish (FIN)

AF:

0.544

AC:

29037

AN:

53418

Middle Eastern (MID)

AF:

0.644

AC:

3715

AN:

5768

European-Non Finnish (NFE)

AF:

0.590

AC:

655640

AN:

1111884

Other (OTH)

AF:

0.632

AC:

38157

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19182

38364

57546

76728

95910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.683

AC:

103632

AN:

151838

Hom.:

36625

Cov.:

AF XY:

0.680

AC XY:

50404

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.878

AC:

36392

AN:

41466

American (AMR)

AF:

0.674

AC:

10286

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

2093

AN:

3466

East Asian (EAS)

AF:

0.763

AC:

3916

AN:

5134

South Asian (SAS)

AF:

0.614

AC:

2958

AN:

4814

European-Finnish (FIN)

AF:

0.537

AC:

5640

AN:

10502

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40207

AN:

67896

Other (OTH)

AF:

0.680

AC:

1429

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1554

3108

4662

6216

7770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.622

Hom.:

153945

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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) -

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

(source)

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;.;.;.

PhyloP100

3.5

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

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.023

gMVP

0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr3-184100628-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over