Variant chr1-248592950-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004693.2(OR2T10):c.819G>T(p.Met273Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,423,642 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000056 ( 1 hom. )

Consequence

OR2T10
NM_001004693.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.97

Variant links:

Genes affected

OR2T10 (HGNC:19573): (olfactory receptor family 2 subfamily T member 10) 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]

OR2T10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052914083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T10	NM_001004693.2 linkuse as main transcript	c.819G>T	p.Met273Ile	missense_variant	2/2	ENST00000642090.1	NP_001004693.1	Q8NGZ9A0A126GV79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T10	ENST00000642090.1 linkuse as main transcript	c.819G>T	p.Met273Ile	missense_variant	2/2		NM_001004693.2	ENSP00000493236.1		Q8NGZ9
OR2T10	ENST00000330500.4 linkuse as main transcript	c.819G>T	p.Met273Ile	missense_variant	1/1	6		ENSP00000329210.2		Q8NGZ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244722

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

1423642

Hom.:

Cov.:

AF XY:

0.00000705

AC XY:

AN XY:

708952

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:

0.00000737

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000843

AC:

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

Aug 08, 2023

The c.819G>T (p.M273I) alteration is located in exon 1 (coding exon 1) of the OR2T10 gene. This alteration results from a G to T substitution at nucleotide position 819, causing the methionine (M) at amino acid position 273 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.33

DANN

Benign

0.51

DEOGEN2

Benign

0.0014

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.13

.;T

M_CAP

Benign

0.00099

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.010

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.060

.;N

REVEL

Benign

0.0040

Sift

Benign

0.23

.;T

Sift4G

Benign

0.58

.;T

Polyphen

0.0020

B;B

Vest4

0.054

MutPred

0.34

Loss of catalytic residue at M273 (P = 0.0247);Loss of catalytic residue at M273 (P = 0.0247);

MVP

0.088

MPC

0.064

ClinPred

0.037

GERP RS

-1.1

Varity_R

0.057

gMVP

0.054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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