1-248061040-A-G

Position:

• chr1-248061040-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004687.2(OR2L3):​c.359A>G​(p.Asp120Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR2L3 NM_001004687.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.45

Genes affected

OR2L3 (HGNC:15009): (olfactory receptor family 2 subfamily L member 3) 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]

OR2L13 (HGNC:19578): (olfactory receptor family 2 subfamily L member 13) 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]

LOC105373275 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2L3	NM_001004687.2	c.359A>G	p.Asp120Gly	missense_variant	2/2	ENST00000359959.4	NP_001004687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2L3	ENST00000359959.4	c.359A>G	p.Asp120Gly	missense_variant	2/2	6	NM_001004687.2	ENSP00000353044.3
OR2L3	ENST00000641161.1	c.359A>G	p.Asp120Gly	missense_variant	2/2			ENSP00000493424.1
OR2L3	ENST00000641649.1	c.359A>G	p.Asp120Gly	missense_variant	3/3			ENSP00000493020.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Jun 01, 2023

The c.359A>G (p.D120G) alteration is located in exon 1 (coding exon 1) of the OR2L3 gene. This alteration results from a A to G substitution at nucleotide position 359, causing the aspartic acid (D) at amino acid position 120 to be replaced by a glycine (G). 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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.059	T;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	.;.;D
M_CAP	Benign	0.0022	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	4.0	H;H;H
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-6.5	D;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.0090	D;.;.
Sift4G	Pathogenic	0.0010	D;.;.
Polyphen		0.11	B;B;B
Vest4		0.45
MutPred		0.74		Gain of methylation at R121 (P = 0.1079);Gain of methylation at R121 (P = 0.1079);Gain of methylation at R121 (P = 0.1079);
MVP		0.51
MPC		0.29
ClinPred		0.57	D
GERP RS		0.61
Varity_R		0.60
gMVP		0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs1663612659; hg19: chr1-248224342;