chr1-248061564-G-A

Position:

• chr1-248061564-G-A

Variant summary

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

The NM_001004687.2(OR2L3):​c.883G>A​(p.Glu295Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2L3 NM_001004687.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

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]

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	UniProt
OR2L3	NM_001004687.2	c.883G>A	p.Glu295Lys	missense_variant	2/2	ENST00000359959.4
LOC105373275	XR_949369.3	n.418+3572C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2L3	ENST00000359959.4	c.883G>A	p.Glu295Lys	missense_variant	2/2		NM_001004687.2	P1
OR2L3	ENST00000641161.1	c.883G>A	p.Glu295Lys	missense_variant	2/2			P1
OR2L3	ENST00000641649.1	c.883G>A	p.Glu295Lys	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Dec 20, 2023

The c.883G>A (p.E295K) alteration is located in exon 1 (coding exon 1) of the OR2L3 gene. This alteration results from a G to A substitution at nucleotide position 883, causing the glutamic acid (E) at amino acid position 295 to be replaced by a lysine (K). 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	0.32
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.76	.;.;T
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.3	D;.;.
REVEL	Benign	0.14
Sift	Uncertain	0.016	D;.;.
Sift4G	Uncertain	0.0020	D;.;.
Polyphen		0.078	B;B;B
Vest4		0.26
MutPred		0.72		Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);Gain of MoRF binding (P = 0.0065);
MVP		0.63
MPC		0.21
ClinPred		0.94	D
GERP RS		2.0
Varity_R		0.33
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-248224866;