chr20-62216366-C-A

Variant names:

• chr20-62216366-C-A
• rs3787430
• NM_007232.3:c.978G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_007232.3(HRH3):​c.978G>T​(p.Pro326Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: HRH3 NM_007232.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.51
• Publications: 17 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11307955).
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HRH3	NM_007232.3	c.978G>T	p.Pro326Pro	synonymous_variant	Exon 3 of 3	ENST00000340177.10	NP_009163.2
HRH3	XM_005260266.4	c.978G>T	p.Pro326Pro	synonymous_variant	Exon 3 of 4		XP_005260323.1
HRH3	XM_017027623.2	c.936G>T	p.Pro312Pro	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	c.978G>T	p.Pro326Pro	synonymous_variant	Exon 3 of 3	1	NM_007232.3	ENSP00000342560.5
HRH3	ENST00000317393.10	c.822-84G>T		intron_variant	Intron 3 of 4	1		ENSP00000321482.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1398

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.049
DANN	Benign	0.70
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.11	T
PhyloP100		-4.5
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MVP		0.70
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

Other links and lift over

dbSNP: rs3787430; hg19: chr20-60791422;