NM_001005482.2:c.605T>G

Variant names:

• chr3-98283507-T-G
• rs140217206
• NM_001005482.2:c.605T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005482.2(OR5H2):​c.605T>G​(p.Leu202Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: OR5H2 NM_001005482.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.249
• Publications: 2 publications found

Genes affected

OR5H2 (HGNC:14752): (olfactory receptor family 5 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]

ENSG00000251088 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060983032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005482.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5H2	NM_001005482.2	MANE Select	c.605T>G	p.Leu202Trp	missense	Exon 1 of 1	NP_001005482.2	Q8NGV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5H2	ENST00000355273.3	TSL:6 MANE Select	c.605T>G	p.Leu202Trp	missense	Exon 1 of 1	ENSP00000347418.3	Q8NGV7
	ENSG00000251088	ENST00000508616.1	TSL:1	n.27-28379T>G		intron	N/A
	ENSG00000289509	ENST00000688712.2		n.129-6032A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 250008 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000678

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1460696 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 726710

African (AFR) AF: 0.000360 AC: 12 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111744

Other (OTH) AF: 0.0000497 AC: 3 AN: 60332

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74352

African (AFR) AF: 0.000579 AC: 24 AN: 41452

American (AMR) AF: 0.000131 AC: 2 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000762 Hom.: 0

Bravo AF: 0.000257

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.25
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.28
MVP		0.58
MPC		0.14
ClinPred		0.12	T
GERP RS		1.9
Varity_R		0.38
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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: rs140217206; hg19: chr3-98002351;