Genetic Variant HTR3A:c.265-72C>T (chr11-113981131-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000869.6(HTR3A):c.265-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 925,392 control chromosomes in the GnomAD database, including 2,833 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 0.058 ( 380 hom., cov: 32)

Exomes 𝑓: 0.073 ( 2453 hom. )

Consequence

HTR3A
NM_000869.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.725

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR3A	NM_000869.6 link	c.265-72C>T	intron_variant	Intron 3 of 8	ENST00000504030.7	NP_000860.3	P46098-1B4E398
HTR3A	NM_213621.4 link	c.265-72C>T	intron_variant	Intron 3 of 7		NP_998786.3	P46098-2B4E398
HTR3A	NM_001161772.3 link	c.220-72C>T	intron_variant	Intron 3 of 8		NP_001155244.1	P46098-3
HTR3A	NR_046363.2 link	n.483-72C>T	intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7 link	c.265-72C>T		intron_variant	Intron 3 of 8	1	NM_000869.6	ENSP00000424189.2		P46098-1

Frequencies

GnomAD3 genomes

AF:

0.0577

AC:

8780

AN:

152208

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0490

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0639

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0526

GnomAD4 exome

AF:

0.0734

AC:

56739

AN:

773066

Hom.:

2453

Cov.:

AF XY:

0.0727

AC XY:

29832

AN XY:

410092

show subpopulations

African (AFR)

AF:

0.0134

AC:

275

AN:

20460

American (AMR)

AF:

0.0695

AC:

2869

AN:

41292

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

667

AN:

21646

East Asian (EAS)

AF:

0.000663

AC:

AN:

36222

South Asian (SAS)

AF:

0.0724

AC:

5098

AN:

70456

European-Finnish (FIN)

AF:

0.130

AC:

6792

AN:

52144

Middle Eastern (MID)

AF:

0.0375

AC:

112

AN:

2988

European-Non Finnish (NFE)

AF:

0.0784

AC:

38411

AN:

490046

Other (OTH)

AF:

0.0659

AC:

2491

AN:

37812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2730

5460

8190

10920

13650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.0576

AC:

8778

AN:

152326

Hom.:

380

Cov.:

AF XY:

0.0593

AC XY:

4418

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0145

AC:

601

AN:

41580

American (AMR)

AF:

0.0490

AC:

749

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5184

South Asian (SAS)

AF:

0.0640

AC:

309

AN:

4830

European-Finnish (FIN)

AF:

0.135

AC:

1437

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5413

AN:

68022

Other (OTH)

AF:

0.0516

AC:

109

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

411

823

1234

1646

2057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0622

Hom.:

558

Bravo

AF:

0.0487

Asia WGS

AF:

0.0300

AC:

106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.4

(source)

DANN

Benign

0.81

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over