Variant 7-144232678-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001001802.3(OR2A42):c.166A>C(p.Thr56Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000093 ( 0 hom., cov: 15)

Exomes 𝑓: 0.00022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A42
NM_001001802.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.862

Variant links:

Genes affected

OR2A42 (HGNC:31230): (olfactory receptor family 2 subfamily A member 42) 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]

OR2A42 links:

ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)

ARHGEF35-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.42243397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2A42	NM_001001802.3 linkuse as main transcript	c.166A>C	p.Thr56Pro	missense_variant	3/3	ENST00000641810.1
ARHGEF35-AS1	NR_126022.1 linkuse as main transcript	n.493+24874T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2A42	ENST00000641810.1 linkuse as main transcript	c.166A>C	p.Thr56Pro	missense_variant	3/3		NM_001001802.3	P1
ARHGEF35-AS1	ENST00000460955.5 linkuse as main transcript	n.493+24874T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000927

AC:

AN:

107820

Hom.:

Cov.:

show subpopulations

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:

0.000146

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000223

AC:

141

AN:

632360

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

339044

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000148

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000154

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000344

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.00000927

AC:

AN:

107886

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

51232

show subpopulations

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:

0.000146

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 01, 2023

The c.166A>C (p.T56P) alteration is located in exon 1 (coding exon 1) of the OR2A42 gene. This alteration results from a A to C substitution at nucleotide position 166, causing the threonine (T) at amino acid position 56 to be replaced by a proline (P). 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

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.012

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.86

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.8

.;D

REVEL

Benign

0.18

Sift

Uncertain

0.0010

.;D

Sift4G

Pathogenic

0.0010

.;D

Vest4

0.54

MutPred

0.70

Gain of glycosylation at P57 (P = 0.1204);Gain of glycosylation at P57 (P = 0.1204);

MVP

0.13

ClinPred

0.93

GERP RS

2.8

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over