Genetic Variant HRH3:p.Ser332Ser (chr20-62216348-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007232.3(HRH3):c.996G>A(p.Ser332Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,592,330 control chromosomes in the GnomAD database, including 136,962 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 0.45 ( 15747 hom., cov: 33)

Exomes 𝑓: 0.41 ( 121215 hom. )

Consequence

HRH3
NM_007232.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.87

Variant links:

Genes affected

HRH3 (HGNC:5184): (histamine receptor H3) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. This gene encodes one of the histamine receptors (H3) which belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [provided by RefSeq, Jul 2008]

HRH3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.982573E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRH3	NM_007232.3 link	c.996G>A	p.Ser332Ser	synonymous_variant	Exon 3 of 3	ENST00000340177.10	NP_009163.2	Q9Y5N1-1
HRH3	XM_005260266.4 link	c.996G>A	p.Ser332Ser	synonymous_variant	Exon 3 of 4		XP_005260323.1	Q9Y5N1-2
HRH3	XM_017027623.2 link	c.954G>A	p.Ser318Ser	synonymous_variant	Exon 3 of 4		XP_016883112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HRH3	ENST00000340177.10 link	c.996G>A	p.Ser332Ser	synonymous_variant	Exon 3 of 3	1	NM_007232.3	ENSP00000342560.5		Q9Y5N1-1
HRH3	ENST00000317393.10 link	c.822-66G>A		intron_variant	Intron 3 of 4	1		ENSP00000321482.7		A0A0A0MR48

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68060

AN:

151942

Hom.:

15713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.447

AC:

98502

AN:

220444

Hom.:

22236

AF XY:

0.443

AC XY:

53145

AN XY:

119914

show subpopulations

Gnomad AFR exome

AF:

0.573

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.536

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.423

GnomAD4 exome

AF:

0.407

AC:

586049

AN:

1440268

Hom.:

121215

Cov.:

AF XY:

0.410

AC XY:

292354

AN XY:

713928

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.524

Gnomad4 FIN exome

AF:

0.419

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.448

AC:

68148

AN:

152062

Hom.:

15747

Cov.:

AF XY:

0.449

AC XY:

33382

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.555

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.343

Gnomad4 SAS

AF:

0.531

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.392

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.393

Hom.:

13896

Bravo

AF:

0.456

TwinsUK

AF:

0.389

AC:

1444

ALSPAC

AF:

0.390

AC:

1502

ESP6500AA

AF:

0.547

AC:

2403

ESP6500EA

AF:

0.395

AC:

3387

ExAC

AF:

0.426

AC:

51112

Asia WGS

AF:

0.481

AC:

1671

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.21

DANN

Benign

0.80

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000080

Vest4

0.050

GERP RS

-9.2

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

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