11-56105613-G-A

Position:

• chr11-56105613-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386064.1(OR8H2):​c.571G>A​(p.Asp191Asn) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR8H2 NM_001386064.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

Genes affected

OR8H2 (HGNC:15308): (olfactory receptor family 8 subfamily H member 2) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25071937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8H2	NM_001386064.1	c.571G>A	p.Asp191Asn	missense_variant	2/2	ENST00000313503.2	NP_001372993.1
OR8H2	NM_001005200.2	c.571G>A	p.Asp191Asn	missense_variant	2/2		NP_001005200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8H2	ENST00000313503.2	c.571G>A	p.Asp191Asn	missense_variant	2/2	6	NM_001386064.1	ENSP00000323982.1
OR8H2	ENST00000641311.1	c.571G>A	p.Asp191Asn	missense_variant	2/2			ENSP00000493031.1
OR8H2	ENST00000618136.1	c.568G>A	p.Asp190Asn	missense_variant	1/1	6		ENSP00000482661.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.571G>A (p.D191N) alteration is located in exon 1 (coding exon 1) of the OR8H2 gene. This alteration results from a G to A substitution at nucleotide position 571, causing the aspartic acid (D) at amino acid position 191 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0060	T;T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.6	D;.;.
REVEL	Benign	0.089
Sift	Benign	0.063	T;.;.
Sift4G	Uncertain	0.060	T;.;T
Polyphen		0.53	P;P;.
Vest4		0.21
MutPred		0.46		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);.;
MVP		0.49
MPC		0.22
ClinPred		0.86	D
GERP RS		2.4
Varity_R		0.21
gMVP		0.047

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: rs1854043469; hg19: chr11-55873089;