6-29440493-C-T

Position:

chr6-29440493-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013941.4(OR10C1):c.478C>T(p.Pro160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 1,613,438 control chromosomes in the GnomAD database, including 3,732 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.098 ( 1346 hom., cov: 32)

Exomes 𝑓: 0.041 ( 2386 hom. )

Consequence

OR10C1
NM_013941.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041463077).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4 linkuse as main transcript	c.478C>T	p.Pro160Ser	missense_variant	1/1	ENST00000444197.3	NP_039229.3	Q96KK4A0A126GV80
OR11A1	NM_001394828.1 linkuse as main transcript	c.-388-8506G>A		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR10C1	ENST00000444197.3 linkuse as main transcript	c.478C>T	p.Pro160Ser	missense_variant	1/1	6	NM_013941.4	ENSP00000419119.1	Q96KK4
OR11A1	ENST00000377149.5 linkuse as main transcript	c.-388-8506G>A		intron_variant		6	NM_001394828.1	ENSP00000366354.1	Q9GZK7
OR10C1	ENST00000622521.1 linkuse as main transcript	c.484C>T	p.Pro162Ser	missense_variant	1/1	6		ENSP00000481429.1	A0A087WY02

Frequencies

GnomAD3 genomes

AF:

0.0975

AC:

14822

AN:

152062

Hom.:

1336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0923

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.0772

Gnomad SAS

AF:

0.0588

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0552

AC:

13611

AN:

246696

Hom.:

730

AF XY:

0.0506

AC XY:

6793

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.0692

Gnomad ASJ exome

AF:

0.0938

Gnomad EAS exome

AF:

0.0501

Gnomad SAS exome

AF:

0.0463

Gnomad FIN exome

AF:

0.0209

Gnomad NFE exome

AF:

0.0318

Gnomad OTH exome

AF:

0.0585

GnomAD4 exome

AF:

0.0409

AC:

59762

AN:

1461258

Hom.:

2386

Cov.:

AF XY:

0.0407

AC XY:

29593

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.0730

Gnomad4 ASJ exome

AF:

0.0936

Gnomad4 EAS exome

AF:

0.0825

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0298

Gnomad4 OTH exome

AF:

0.0597

GnomAD4 genome

AF:

0.0976

AC:

14856

AN:

152180

Hom.:

1346

Cov.:

AF XY:

0.0945

AC XY:

7034

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.0921

Gnomad4 ASJ

AF:

0.0968

Gnomad4 EAS

AF:

0.0766

Gnomad4 SAS

AF:

0.0580

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0423

Hom.:

415

Bravo

AF:

0.110

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0293

AC:

113

ESP6500AA

AF:

0.230

AC:

696

ESP6500EA

AF:

0.0340

AC:

184

ExAC

AF:

0.0551

AC:

6592

Asia WGS

AF:

0.0760

AC:

265

AN:

3478

EpiCase

AF:

0.0370

EpiControl

AF:

0.0392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.016

DANN

Benign

0.64

DEOGEN2

Benign

0.0012

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0071

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.4

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

2.0

N;.

REVEL

Benign

0.038

Sift

Benign

0.48

T;.

Polyphen

0.0

B;.

MPC

0.34

ClinPred

0.000017

GERP RS

0.87

Varity_R

0.038

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over