11-5986089-C-A

Position:

• chr11-5986089-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001005173.3(OR52L1):​c.842G>T​(p.Arg281Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R281H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR52L1 NM_001005173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

OR52L1 (HGNC:14785): (olfactory receptor family 52 subfamily L 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]

OR56A3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52L1	NM_001005173.3	c.842G>T	p.Arg281Leu	missense_variant	1/1	ENST00000332249.4
OR56A3	XM_047426926.1	c.*469-17631C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52L1	ENST00000332249.4	c.842G>T	p.Arg281Leu	missense_variant	1/1		NM_001005173.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

Oct 03, 2022

The c.842G>T (p.R281L) alteration is located in exon 1 (coding exon 1) of the OR52L1 gene. This alteration results from a G to T substitution at nucleotide position 842, causing the arginine (R) at amino acid position 281 to be replaced by a leucine (L). 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
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.47	N
M_CAP	Benign	0.0042	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	0.85	N
PrimateAI	Benign	0.16	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.56
MutPred		0.72		Loss of catalytic residue at R281 (P = 0.0077);
MVP		0.51
MPC		0.20
ClinPred		0.97	D
GERP RS		2.2
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-6007319;