1-248061568-T-G

Variant names:

• chr1-248061568-T-G
• rs773053358
• NM_001004687.2:c.887T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001004687.2(OR2L3):​c.887T>G​(p.Val296Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V296E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2L3 NM_001004687.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2L3	NM_001004687.2	c.887T>G	p.Val296Gly	missense_variant	Exon 2 of 2	ENST00000359959.4	NP_001004687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2L3	ENST00000359959.4	c.887T>G	p.Val296Gly	missense_variant	Exon 2 of 2	6	NM_001004687.2	ENSP00000353044.3
OR2L3	ENST00000641161.1	c.887T>G	p.Val296Gly	missense_variant	Exon 2 of 2			ENSP00000493424.1
OR2L3	ENST00000641649.1	c.887T>G	p.Val296Gly	missense_variant	Exon 3 of 3			ENSP00000493020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.93	.;.;D
M_CAP	Benign	0.0047	T
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Pathogenic	3.3	M;M;M
PhyloP100		4.1
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-6.1	D;.;.
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;.;.
Sift4G	Pathogenic	0.0	D;.;.
Polyphen		1.0	D;D;D
Vest4		0.41
MutPred		0.82		Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);
MVP		0.46
MPC		0.59
ClinPred		0.98	D
GERP RS		1.9
Varity_R		0.81
gMVP		0.24
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs773053358; hg19: chr1-248224870;