Genetic Variant OR2C3:p.Ala203Asp (chr1-247531904-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198074.6(OR2C3):c.608C>A(p.Ala203Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A203G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR2C3
NM_198074.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.210

Variant links:

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]

OR2C3 links:

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]

GCSAML links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32416412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2C3	NM_198074.6 link	c.608C>A	p.Ala203Asp	missense_variant	Exon 3 of 3	ENST00000641802.1	NP_932340.4	Q8N628

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2C3	ENST00000641802.1 link	c.608C>A	p.Ala203Asp	missense_variant	Exon 3 of 3		NM_198074.6	ENSP00000493385.1		Q8N628

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;.

Eigen

Benign

0.097

Eigen_PC

Benign

0.031

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.33

.;.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-4.1

.;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.010

.;D;.

Sift4G

Benign

0.069

.;T;T

Polyphen

0.87

P;P;.

Vest4

0.46, 0.45

MutPred

0.54

Gain of phosphorylation at Y201 (P = 0.1151);Gain of phosphorylation at Y201 (P = 0.1151);Gain of phosphorylation at Y201 (P = 0.1151);

MVP

0.47

MPC

0.47

ClinPred

0.95

GERP RS

3.8

Varity_R

0.58

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over