6-29440751-A-T

Variant names:

Variant summary

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

The NM_013941.4(OR10C1):c.736A>T(p.Met246Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 1,613,746 control chromosomes in the GnomAD database, including 1,173 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.051 ( 380 hom., cov: 32)

Exomes 𝑓: 0.020 ( 793 hom. )

Consequence

OR10C1
NM_013941.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.538

Publications

34 publications found

Variant links:

Genes affected

OR10C1 (HGNC:8165): (olfactory receptor family 10 subfamily C 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

OR10C1 links:

OR11A1 (HGNC:8176): (olfactory receptor family 11 subfamily A 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]

OR11A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.002963245).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10C1	NM_013941.4 link	c.736A>T	p.Met246Leu	missense_variant	Exon 1 of 1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1 link	c.-388-8764T>A		intron_variant	Intron 1 of 4	ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
OR10C1	ENST00000444197.3 link	c.736A>T	p.Met246Leu	missense_variant	Exon 1 of 1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5 link	c.-388-8764T>A		intron_variant	Intron 1 of 4	6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1 link	c.742A>T	p.Met248Leu	missense_variant	Exon 1 of 1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes

AF:

0.0506

AC:

7689

AN:

151994

Hom.:

378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0637

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.0392

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.00435

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0636

GnomAD2 exomes

AF:

0.0281

AC:

7005

AN:

248988

AF XY:

0.0254

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0467

Gnomad ASJ exome

AF:

0.0728

Gnomad EAS exome

AF:

0.0155

Gnomad FIN exome

AF:

0.00490

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0334

GnomAD4 exome

AF:

0.0201

AC:

29319

AN:

1461632

Hom.:

793

Cov.:

AF XY:

0.0200

AC XY:

14573

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.127

AC:

4236

AN:

33456

American (AMR)

AF:

0.0482

AC:

2156

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0715

AC:

1868

AN:

26130

East Asian (EAS)

AF:

0.0664

AC:

2636

AN:

39700

South Asian (SAS)

AF:

0.0200

AC:

1728

AN:

86256

European-Finnish (FIN)

AF:

0.00464

AC:

248

AN:

53392

Middle Eastern (MID)

AF:

0.0680

AC:

392

AN:

5764

European-Non Finnish (NFE)

AF:

0.0128

AC:

14221

AN:

1111824

Other (OTH)

AF:

0.0304

AC:

1834

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1712

3425

5137

6850

8562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.0507

AC:

7715

AN:

152114

Hom.:

380

Cov.:

AF XY:

0.0489

AC XY:

3636

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.121

AC:

5010

AN:

41530

American (AMR)

AF:

0.0637

AC:

974

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0741

AC:

257

AN:

3468

East Asian (EAS)

AF:

0.0393

AC:

202

AN:

5144

South Asian (SAS)

AF:

0.0191

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00435

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

979

AN:

67960

Other (OTH)

AF:

0.0625

AC:

132

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

358

715

1073

1430

1788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.00120

Hom.:

52755

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0112

AC:

ExAC

AF:

0.0279

AC:

3381

EpiCase

AF:

0.0202

EpiControl

AF:

0.0204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.00065

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.0

.;.

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.27

N;.

PhyloP100

0.54

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.030

N;.

REVEL

Benign

0.074

Sift

Uncertain

0.0020

D;.

Sift4G

Pathogenic

0.0

.;.

Vest4

0.0

ClinPred

0.0094

GERP RS

3.5

Varity_R

0.39

gMVP

0.15

Mutation Taster

=96/4

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