NM_001005479.2:c.292A>C

Variant names:

• chr3-98264624-A-C
• rs767850975
• NM_001005479.2:c.292A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005479.2(OR5H6):​c.292A>C​(p.Met98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000706 in 141,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M98V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000071 (0 hom., cov: 32)
• Consequence: OR5H6 NM_001005479.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 2 publications found

Genes affected

OR5H6 (HGNC:14767): (olfactory receptor family 5 subfamily H member 6) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

ENSG00000251088 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052372187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005479.2. 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
	OR5H6	NM_001005479.2	MANE Select	c.292A>C	p.Met98Leu	missense	Exon 1 of 1	NP_001005479.2	A0A126GW86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5H6	ENST00000615035.3	TSL:6 MANE Select	c.292A>C	p.Met98Leu	missense	Exon 1 of 1	ENSP00000480705.3	A0A126GW86
	ENSG00000251088	ENST00000508616.1	TSL:1	n.26+30948A>C		intron	N/A
	OR5H6	ENST00000642105.1		c.340A>C	p.Met114Leu	missense	Exon 1 of 1	ENSP00000493340.1	Q8NGV6

Frequencies

GnomAD3 genomes AF: 0.00000706 AC: 1 AN: 141572 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 44

GnomAD4 genome AF: 0.00000706 AC: 1 AN: 141572 Hom.: 0 Cov.: 32 AF XY: 0.0000145 AC XY: 1 AN XY: 69046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000248 AC: 1 AN: 40336

American (AMR) AF: 0.00 AC: 0 AN: 14084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3234

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61850

Other (OTH) AF: 0.00 AC: 0 AN: 1912

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.34
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.00081	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.040	N
PhyloP100		-0.66
PrimateAI	Benign	0.23	T
Polyphen		0.0010	B
MutPred		0.41		Gain of catalytic residue at M114 (P = 0.1778)
ClinPred		0.041	T
GERP RS		2.2
PromoterAI		0.0040	Neutral
Varity_R		0.31
gMVP		0.16
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: rs767850975; hg19: chr3-97983468;