Variant 1-248559473-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004694.3(OR2T29):c.19A>T(p.Met7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 1,586,660 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000069 ( 1 hom. )

Consequence

OR2T29
NM_001004694.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.21

Variant links:

Genes affected

OR2T29 (HGNC:31253): (olfactory receptor family 2 subfamily T member 29) 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]

OR2T29 links:

ENSG00000224521 (HGNC:):

ENSG00000224521 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T29	NM_001004694.3 link	c.19A>T	p.Met7Leu	missense_variant	2/2	ENST00000641069.1	NP_001004694.2	Q8NH02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR2T29	ENST00000641069.1 link	c.19A>T	p.Met7Leu	missense_variant	2/2		NM_001004694.3	ENSP00000492895.1	Q8NH02
OR2T29	ENST00000328570.6 link	c.19A>T	p.Met7Leu	missense_variant	1/1	6		ENSP00000331774.3	Q8NH02
ENSG00000224521	ENST00000438623.1 link	n.92-3127T>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000748

AC:

AN:

133666

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000166

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1452994

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

722716

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:

0.00000904

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000748

AC:

AN:

133666

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

64366

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:

0.00

Gnomad4 NFE

AF:

0.0000166

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

Mar 25, 2024

The c.19A>T (p.M7L) alteration is located in exon 1 (coding exon 1) of the OR2T29 gene. This alteration results from a A to T substitution at nucleotide position 19, causing the methionine (M) at amino acid position 7 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.7

DANN

Benign

0.50

DEOGEN2

Benign

0.0040

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.29

.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.16

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.78

.;N

REVEL

Benign

0.013

Sift

Benign

0.29

.;T

Sift4G

Benign

0.97

.;T

Polyphen

0.0

B;B

Vest4

0.10

MutPred

0.28

Loss of disorder (P = 0.0978);Loss of disorder (P = 0.0978);

MVP

0.33

MPC

1.8

ClinPred

0.077

GERP RS

-4.7

Varity_R

0.060

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: 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