20-62216366-C-G

Position:

• chr20-62216366-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_007232.3(HRH3):​c.978G>C​(p.Pro326Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,419,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: HRH3 NM_007232.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.51

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10406646).
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRH3	NM_007232.3	c.978G>C	p.Pro326Pro	synonymous_variant	3/3	ENST00000340177.10	NP_009163.2
HRH3	XM_005260266.4	c.978G>C	p.Pro326Pro	synonymous_variant	3/4		XP_005260323.1
HRH3	XM_017027623.2	c.936G>C	p.Pro312Pro	synonymous_variant	3/4		XP_016883112.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRH3	ENST00000340177.10	c.978G>C	p.Pro326Pro	synonymous_variant	3/3	1	NM_007232.3	ENSP00000342560.5
HRH3	ENST00000317393.10	c.822-84G>C		intron_variant		1		ENSP00000321482.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000539 AC: 1 AN: 185610 Hom.: 0 AF XY: 0.00000996 AC XY: 1 AN XY: 100444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000129

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000352 AC: 5 AN: 1419182 Hom.: 0 Cov.: 35 AF XY: 0.00000285 AC XY: 2 AN XY: 701428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.052
DANN	Benign	0.60
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.10	T
Sift4G	Pathogenic	0.0	D
Vest4		0.17
MVP		0.72
GERP RS		-9.1

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

Other links and lift over

dbSNP: rs3787430; hg19: chr20-60791422;