11-5132269-T-C

Variant names:

• chr11-5132269-T-C
• rs149098448
• NM_001005160.3:c.374A>G

Variant summary

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

The NM_001005160.3(OR52A5):​c.374A>G​(p.Tyr125Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. Y125F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (1 hom.)
• Consequence: OR52A5 NM_001005160.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 5 publications found

Genes affected

OR52A5 (HGNC:19580): (olfactory receptor family 52 subfamily A member 5) 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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.065526426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005160.3. 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
	OR52A5	NM_001005160.3	MANE Select	c.374A>G	p.Tyr125Cys	missense	Exon 2 of 2	NP_001005160.1	A0A126GWD2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52A5	ENST00000307388.2	TSL:6 MANE Select	c.374A>G	p.Tyr125Cys	missense	Exon 2 of 2	ENSP00000303469.1	Q9H2C5
	OR52A5	ENST00000642125.1		c.374A>G	p.Tyr125Cys	missense	Exon 2 of 2	ENSP00000493298.1	Q9H2C5

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.000647

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000426 AC: 107 AN: 251434 AF XY: 0.000442

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000577 AC: 844 AN: 1461886 Hom.: 1 Cov.: 33 AF XY: 0.000572 AC XY: 416 AN XY: 727242

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000713 AC: 793 AN: 1112006

Other (OTH) AF: 0.000397 AC: 24 AN: 60396

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74458

African (AFR) AF: 0.000265 AC: 11 AN: 41562

American (AMR) AF: 0.000523 AC: 8 AN: 15288

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000635 Hom.: 0

Bravo AF: 0.000548

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000682 AC: 3

ESP6500EA AF: 0.000931 AC: 8

ExAC AF: 0.000428 AC: 52

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Uncertain	0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.016
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.15
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.024	D
Polyphen		0.34	B
Vest4		0.36
MVP		0.52
MPC		0.0099
ClinPred		0.11	T
GERP RS		5.2
Varity_R		0.40
gMVP		0.41
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149098448; hg19: chr11-5153499;