Genetic Variant NM_206899.1:c.137T>C (chr12-55637028-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_206899.1(OR10P1):c.137T>C(p.Ile46Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000321 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

OR10P1
NM_206899.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Publications

4 publications found

Variant links:

Genes affected

OR10P1 (HGNC:15378): (olfactory receptor family 10 subfamily P member 1) 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]

OR10P1 links:

ENSG00000258763 (HGNC:):

ENSG00000258763 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08492631).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206899.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10P1	NM_206899.1	MANE Select	c.137T>C	p.Ile46Thr	missense	Exon 1 of 1	NP_996782.1	Q8NGE3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR10P1	ENST00000309675.3	TSL:6 MANE Select	c.137T>C	p.Ile46Thr	missense	Exon 1 of 1	ENSP00000308082.2	Q8NGE3
ENSG00000258763	ENST00000715996.1		n.493+1886A>G		intron	N/A
ENSG00000258763	ENST00000804081.1		n.231+366A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000270

AC:

AN:

251486

AF XY:

0.000309

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000329

AC:

481

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

248

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000396

AC:

440

AN:

1111976

Other (OTH)

AF:

0.000315

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000244

AC:

AN:

151938

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.0000726

AC:

AN:

41342

American (AMR)

AF:

0.000393

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

67962

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000462

Hom.:

Bravo

AF:

0.000355

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.038

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.71

M_CAP

Benign

0.0021

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PhyloP100

3.8

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.11

Sift

Benign

0.035

Sift4G

Uncertain

0.039

Polyphen

0.26

Vest4

0.37

MVP

0.43

MPC

0.14

ClinPred

0.036

GERP RS

4.3

PromoterAI

-0.0046

Neutral

(source)

Varity_R

0.32

gMVP

0.39

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over