Genetic Variant OR2T34:p.Val145Glu (chr1-248574324-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001001821.1(OR2T34):c.434T>A(p.Val145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000694 in 1,441,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

OR2T34
NM_001001821.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.174

Variant links:

Genes affected

OR2T34 (HGNC:31256): (olfactory receptor family 2 subfamily T member 34) 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]

OR2T34 links:

ENSG00000229255 (HGNC:):

ENSG00000229255 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T34	NM_001001821.1 link	c.434T>A	p.Val145Glu	missense_variant	Exon 1 of 1	ENST00000328782.3	NP_001001821.1	Q8NGX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T34	ENST00000328782.3 link	c.434T>A	p.Val145Glu	missense_variant	Exon 1 of 1	6	NM_001001821.1	ENSP00000330904.2		Q8NGX1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000694

AC:

AN:

1441632

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

717730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32466

American (AMR)

AF:

0.00

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.000252

AC:

AN:

39606

South Asian (SAS)

AF:

0.00

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094670

Other (OTH)

AF:

0.00

AC:

AN:

59706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.434T>A (p.V145E) alteration is located in exon 1 (coding exon 1) of the OR2T34 gene. This alteration results from a T to A substitution at nucleotide position 434, causing the valine (V) at amino acid position 145 to be replaced by a glutamic acid (E). 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

0.28

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.85

M_CAP

Benign

0.00052

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.98

MutationAssessor

Pathogenic

2.9

PhyloP100

-0.17

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.046

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.50

MutPred

0.63

Gain of relative solvent accessibility (P = 0.1259);

MVP

0.38

ClinPred

0.95

GERP RS

2.3

PromoterAI

-0.0050

Neutral

(source)

Varity_R

0.75

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-248574324-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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