1-247532052-G-T

Variant names:

• chr1-247532052-G-T
• rs1477636748
• NM_198074.6:c.460C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198074.6(OR2C3):​c.460C>A​(p.Leu154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. L154V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: OR2C3 NM_198074.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

Genes affected

OR2C3 (HGNC:15005): (olfactory receptor family 2 subfamily C 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]

GCSAML (HGNC:29583): (germinal center associated signaling and motility like) This gene encodes a protein thought to be a signaling molecule associated with germinal centers, the sites of proliferation and differentiation of mature B lymphocytes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22596687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2C3	NM_198074.6	c.460C>A	p.Leu154Met	missense_variant	Exon 3 of 3	ENST00000641802.1	NP_932340.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2C3	ENST00000641802.1	c.460C>A	p.Leu154Met	missense_variant	Exon 3 of 3		NM_198074.6	ENSP00000493385.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0076	T;T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.038
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.23	.;.;T
M_CAP	Benign	0.00068	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.0	.;N;.
REVEL	Benign	0.11
Sift	Benign	0.050	.;D;.
Sift4G	Benign	0.085	.;T;T
Polyphen		1.0	D;D;.
Vest4		0.16, 0.15
MutPred		0.66		Gain of glycosylation at T155 (P = 0.1163);Gain of glycosylation at T155 (P = 0.1163);Gain of glycosylation at T155 (P = 0.1163);
MVP		0.40
MPC		0.35
ClinPred		0.40	T
GERP RS		3.0
Varity_R		0.20
gMVP		0.12

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: rs1477636748; hg19: chr1-247695354;