11-5151624-C-T

Position:

• chr11-5151624-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012375.3(OR52A1):​c.746G>A​(p.Cys249Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR52A1 NM_012375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.418

Genes affected

OR52A1 (HGNC:8318): (olfactory receptor family 52 subfamily A member 1) 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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29367548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52A1	NM_012375.3	c.746G>A	p.Cys249Tyr	missense_variant	2/2	ENST00000380367.3	NP_036507.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52A1	ENST00000380367.3	c.746G>A	p.Cys249Tyr	missense_variant	2/2		NM_012375.3	ENSP00000369725	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.746G>A (p.C249Y) alteration is located in exon 1 (coding exon 1) of the OR52A1 gene. This alteration results from a G to A substitution at nucleotide position 746, causing the cysteine (C) at amino acid position 249 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T
Eigen	Benign	0.0014
Eigen_PC	Benign	-0.056
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.58	.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	0.51	D;D
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.49	P;P
Vest4		0.51
MVP		0.50
MPC		0.058
ClinPred		0.82	D
GERP RS		3.4
Varity_R		0.88
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs369074064; hg19: chr11-5172854;