Genetic Variant NM_001004475.1:c.293G>A (chr1-158399174-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004475.1(OR10T2):c.293G>A(p.Cys98Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,750 control chromosomes in the GnomAD database, including 9,214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.080 ( 628 hom., cov: 33)

Exomes 𝑓: 0.10 ( 8586 hom. )

Consequence

OR10T2
NM_001004475.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45

Publications

16 publications found

Variant links:

Genes affected

OR10T2 (HGNC:14816): (olfactory receptor family 10 subfamily T member 2) 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]

OR10T2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017620325).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10T2	NM_001004475.1 link	c.293G>A	p.Cys98Tyr	missense_variant	Exon 1 of 1	ENST00000334438.1	NP_001004475.1	Q8NGX3A0A126GV74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10T2	ENST00000334438.1 link	c.293G>A	p.Cys98Tyr	missense_variant	Exon 1 of 1	6	NM_001004475.1	ENSP00000334115.1		Q8NGX3

Frequencies

GnomAD3 genomes

AF:

0.0803

AC:

12218

AN:

152136

Hom.:

630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.0845

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0881

GnomAD2 exomes

AF:

0.0994

AC:

24916

AN:

250728

AF XY:

0.107

show subpopulations

Gnomad AFR exome

AF:

0.0184

Gnomad AMR exome

AF:

0.0602

Gnomad ASJ exome

AF:

0.0486

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0994

Gnomad OTH exome

AF:

0.0996

GnomAD4 exome

AF:

0.103

AC:

150266

AN:

1461496

Hom.:

8586

Cov.:

AF XY:

0.106

AC XY:

76931

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.0148

AC:

497

AN:

33478

American (AMR)

AF:

0.0637

AC:

2847

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0473

AC:

1237

AN:

26136

East Asian (EAS)

AF:

0.153

AC:

6081

AN:

39680

South Asian (SAS)

AF:

0.184

AC:

15827

AN:

86238

European-Finnish (FIN)

AF:

0.102

AC:

5439

AN:

53418

Middle Eastern (MID)

AF:

0.148

AC:

855

AN:

5764

European-Non Finnish (NFE)

AF:

0.100

AC:

111271

AN:

1111684

Other (OTH)

AF:

0.103

AC:

6212

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

7405

14810

22215

29620

37025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4118

8236

12354

16472

20590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0802

AC:

12210

AN:

152254

Hom.:

628

Cov.:

AF XY:

0.0821

AC XY:

6111

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0194

AC:

808

AN:

41562

American (AMR)

AF:

0.0842

AC:

1288

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3472

East Asian (EAS)

AF:

0.132

AC:

682

AN:

5172

South Asian (SAS)

AF:

0.194

AC:

936

AN:

4818

European-Finnish (FIN)

AF:

0.102

AC:

1087

AN:

10614

Middle Eastern (MID)

AF:

0.144

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.102

AC:

6932

AN:

68016

Other (OTH)

AF:

0.0867

AC:

183

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

572

1143

1715

2286

2858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0927

Hom.:

1581

Bravo

AF:

0.0736

TwinsUK

AF:

0.102

AC:

378

ALSPAC

AF:

0.0976

AC:

376

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.0995

AC:

856

ExAC

AF:

0.100

AC:

12168

Asia WGS

AF:

0.137

AC:

473

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.8

PhyloP100

7.5

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MPC

0.017

ClinPred

0.10

GERP RS

4.6

PromoterAI

0.026

Neutral

(source)

Varity_R

0.94

gMVP

0.40

Mutation Taster

=83/17

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over