3-98283044-C-T

Variant names:

• chr3-98283044-C-T
• rs183927815
• NM_001005482.2:c.142C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005482.2(OR5H2):​c.142C>T​(p.Leu48Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: OR5H2 NM_001005482.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.75
• Publications: 8 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15551805).

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.142C>T	p.Leu48Phe	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.142C>T	p.Leu48Phe	missense	Exon 1 of 1	ENSP00000347418.3	Q8NGV7
	ENSG00000251088	ENST00000508616.1	TSL:1	n.27-28842C>T		intron	N/A
	ENSG00000289509	ENST00000688712.2		n.129-5569G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.000478

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251304 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.000163

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461726 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111910

Other (OTH) AF: 0.0000828 AC: 5 AN: 60392

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152252 Hom.: 1 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74450

African (AFR) AF: 0.00 AC: 0 AN: 41532

American (AMR) AF: 0.000719 AC: 11 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000170

ExAC AF: 0.00000824 AC: 1

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	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-1.7
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.051
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		0.98	D
Vest4		0.29
MVP		0.46
MPC		0.13
ClinPred		0.92	D
GERP RS		2.3
Varity_R		0.74
gMVP		0.080
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs183927815; hg19: chr3-98001888; COSMIC: COSV62352177;