dbSNP rs33940208: HTR3A:p.Leu10Leu (chr11-113975355-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000869.6(HTR3A):c.30C>T(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 1,613,096 control chromosomes in the GnomAD database, including 4,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.071 ( 844 hom., cov: 33)

Exomes 𝑓: 0.032 ( 3311 hom. )

Consequence

HTR3A
NM_000869.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Publications

15 publications found

Variant links:

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

HTR3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000869.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTR3A	NM_000869.6	MANE Select	c.30C>T	p.Leu10Leu	synonymous	Exon 1 of 9	NP_000860.3	P46098-1
HTR3A	NM_213621.4		c.30C>T	p.Leu10Leu	synonymous	Exon 1 of 8	NP_998786.3	P46098-2
HTR3A	NR_046363.2		n.248C>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.30C>T	p.Leu10Leu	synonymous	Exon 1 of 9	ENSP00000424189.2	P46098-1
HTR3A	ENST00000375498.6	TSL:1	c.48C>T	p.Leu16Leu	synonymous	Exon 1 of 9	ENSP00000364648.2	P46098-4
HTR3A	ENST00000355556.6	TSL:2	c.48C>T	p.Leu16Leu	synonymous	Exon 1 of 8	ENSP00000347754.2	P46098-5

Frequencies

GnomAD3 genomes

AF:

0.0712

AC:

10826

AN:

152154

Hom.:

832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.00989

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0661

GnomAD2 exomes

AF:

0.0821

AC:

20432

AN:

248954

AF XY:

0.0727

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.00947

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.0551

GnomAD4 exome

AF:

0.0321

AC:

46944

AN:

1460824

Hom.:

3311

Cov.:

AF XY:

0.0330

AC XY:

23967

AN XY:

726744

show subpopulations

African (AFR)

AF:

0.142

AC:

4740

AN:

33474

American (AMR)

AF:

0.251

AC:

11208

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.0137

AC:

359

AN:

26134

East Asian (EAS)

AF:

0.155

AC:

6156

AN:

39692

South Asian (SAS)

AF:

0.106

AC:

9180

AN:

86218

European-Finnish (FIN)

AF:

0.00976

AC:

513

AN:

52552

Middle Eastern (MID)

AF:

0.0321

AC:

185

AN:

5768

European-Non Finnish (NFE)

AF:

0.0107

AC:

11853

AN:

1111976

Other (OTH)

AF:

0.0455

AC:

2750

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

2508

5016

7523

10031

12539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0715

AC:

10884

AN:

152272

Hom.:

844

Cov.:

AF XY:

0.0730

AC XY:

5432

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.140

AC:

5824

AN:

41542

American (AMR)

AF:

0.155

AC:

2373

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

955

AN:

5170

South Asian (SAS)

AF:

0.126

AC:

609

AN:

4828

European-Finnish (FIN)

AF:

0.00989

AC:

105

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0120

AC:

814

AN:

68032

Other (OTH)

AF:

0.0725

AC:

153

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

467

935

1402

1870

2337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0415

Hom.:

271

Bravo

AF:

0.0859

Asia WGS

AF:

0.177

AC:

613

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.6

(source)

DANN

Benign

0.80

PhyloP100

-3.0

PromoterAI

-0.029

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over