Variant chr1-248650406-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001824.2(OR2T27):c.479C>T(p.Thr160Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T160N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000018 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR2T27
NM_001001824.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.418

Variant links:

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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]

OR2T27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21175495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T27	NM_001001824.2 linkuse as main transcript	c.479C>T	p.Thr160Ile	missense_variant	2/2	ENST00000460972.4
OR2T27	NM_001386060.1 linkuse as main transcript	c.479C>T	p.Thr160Ile	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T27	ENST00000460972.4 linkuse as main transcript	c.479C>T	p.Thr160Ile	missense_variant	2/2		NM_001001824.2	P1
OR2T27	ENST00000641652.1 linkuse as main transcript	c.479C>T	p.Thr160Ile	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.0000547

AC:

AN:

128082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000770

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:

0.0000703

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000246

AC:

AN:

203066

Hom.:

AF XY:

0.00000914

AC XY:

AN XY:

109354

show subpopulations

Gnomad AFR exome

AF:

0.0000690

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:

0.0000457

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000182

AC:

AN:

1261816

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

635998

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:

0.0000247

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000547

AC:

AN:

128082

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

60726

show subpopulations

Gnomad4 AFR

AF:

0.0000770

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:

0.0000703

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000168

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

Apr 10, 2023

The c.479C>T (p.T160I) alteration is located in exon 1 (coding exon 1) of the OR2T27 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the threonine (T) at amino acid position 160 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

0.25

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.82

.;.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-4.9

.;.;D

REVEL

Benign

0.049

Sift

Benign

0.032

.;.;D

Sift4G

Uncertain

0.037

.;.;D

Polyphen

1.0

D;D;D

Vest4

0.15

MVP

0.46

MPC

1.2

ClinPred

0.39

GERP RS

1.3

Varity_R

0.26

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

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