Genetic Variant HTR3A:c.-42T>C (chr11-113975284-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000869.6(HTR3A):c.-42T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,608,240 control chromosomes in the GnomAD database, including 497,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.72 ( 40471 hom., cov: 33)

Exomes 𝑓: 0.79 ( 456974 hom. )

Consequence

HTR3A
NM_000869.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.396

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=-0.88).

BP6

Variant 11-113975284-T-C is Benign according to our data. Variant chr11-113975284-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR3A	NM_000869.6 link	c.-42T>C	5_prime_UTR_variant	Exon 1 of 9	ENST00000504030.7	NP_000860.3	P46098-1B4E398
HTR3A	NM_213621.4 link	c.-42T>C	5_prime_UTR_variant	Exon 1 of 8		NP_998786.3	P46098-2B4E398
HTR3A	NR_046363.2 link	n.177T>C	non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030 link	c.-42T>C		5_prime_UTR_variant	Exon 1 of 9	1	NM_000869.6	ENSP00000424189.2		P46098-1

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109319

AN:

152034

Hom.:

40441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.536

Gnomad AMI

AF:

0.745

Gnomad AMR

AF:

0.794

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.865

Gnomad SAS

AF:

0.867

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.790

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.734

GnomAD2 exomes

AF:

0.791

AC:

194143

AN:

245414

AF XY:

0.795

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.863

Gnomad ASJ exome

AF:

0.750

Gnomad EAS exome

AF:

0.862

Gnomad FIN exome

AF:

0.763

Gnomad NFE exome

AF:

0.782

Gnomad OTH exome

AF:

0.787

GnomAD4 exome

AF:

0.790

AC:

1150729

AN:

1456088

Hom.:

456974

Cov.:

AF XY:

0.793

AC XY:

574422

AN XY:

724308

show subpopulations

Gnomad4 AFR exome

AF:

0.522

AC:

17456

AN:

33422

Gnomad4 AMR exome

AF:

0.856

AC:

38035

AN:

44426

Gnomad4 ASJ exome

AF:

0.751

AC:

19569

AN:

26062

Gnomad4 EAS exome

AF:

0.874

AC:

34672

AN:

39654

Gnomad4 SAS exome

AF:

0.868

AC:

74506

AN:

85860

Gnomad4 FIN exome

AF:

0.763

AC:

39323

AN:

51526

Gnomad4 NFE exome

AF:

0.789

AC:

875600

AN:

1109160

Gnomad4 Remaining exome

AF:

0.779

AC:

46937

AN:

60230

Heterozygous variant carriers

13555

27111

40666

54222

67777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20618

41236

61854

82472

103090

<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:

0.719

AC:

109399

AN:

152152

Hom.:

40471

Cov.:

AF XY:

0.721

AC XY:

53630

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.536

AC:

0.535716

AN:

0.535716

Gnomad4 AMR

AF:

0.795

AC:

0.794744

AN:

0.794744

Gnomad4 ASJ

AF:

0.750

AC:

0.750432

AN:

0.750432

Gnomad4 EAS

AF:

0.865

AC:

0.865027

AN:

0.865027

Gnomad4 SAS

AF:

0.868

AC:

0.868312

AN:

0.868312

Gnomad4 FIN

AF:

0.759

AC:

0.758735

AN:

0.758735

Gnomad4 NFE

AF:

0.783

AC:

0.783172

AN:

0.783172

Gnomad4 OTH

AF:

0.736

AC:

0.736295

AN:

0.736295

Heterozygous variant carriers

1555

3110

4665

6220

7775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.758

Hom.:

139294

Bravo

AF:

0.714

Asia WGS

AF:

0.861

AC:

2996

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.72

Mutation Taster

=300/0

polymorphism (auto)

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over