chr3-98264441-A-T

Variant names:

• chr3-98264441-A-T
• rs1225216466
• NM_001005479.2:c.109A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005479.2(OR5H6):​c.109A>T​(p.Ile37Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,415,010 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. I37L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: OR5H6 NM_001005479.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09977111).

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.109A>T	p.Ile37Phe	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.109A>T	p.Ile37Phe	missense	Exon 1 of 1	ENSP00000480705.3	A0A126GW86
	ENSG00000251088	ENST00000508616.1	TSL:1	n.26+30765A>T		intron	N/A
	OR5H6	ENST00000642105.1		c.157A>T	p.Ile53Phe	missense	Exon 1 of 1	ENSP00000493340.1	Q8NGV6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1415010 Hom.: 0 Cov.: 49 AF XY: 0.00000142 AC XY: 1 AN XY: 705768

African (AFR) AF: 0.000124 AC: 4 AN: 32174

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.00 AC: 0 AN: 85358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069616

Other (OTH) AF: 0.00 AC: 0 AN: 58806

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.8
PrimateAI	Benign	0.30	T
Polyphen		0.96	D
MutPred		0.32		Loss of stability (P = 0.1204)
ClinPred		0.31	T
GERP RS		-1.1
PromoterAI		0.0042	Neutral
Varity_R		0.19
gMVP		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1225216466; hg19: chr3-97983285;