Genetic Variant NM_001004478.2:c.881A>C (chr1-158607319-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001004478.2(OR10Z1):c.881A>C(p.Asn294Thr) variant causes a missense change. The variant allele was found at a frequency of 0.255 in 1,613,186 control chromosomes in the GnomAD database, including 55,517 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4538 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50979 hom. )

Consequence

OR10Z1
NM_001004478.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

Variant links:

Genes affected

OR10Z1 (HGNC:14996): (olfactory receptor family 10 subfamily Z 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]

OR10Z1 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=0.004341036).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10Z1	NM_001004478.2 link	c.881A>C	p.Asn294Thr	missense_variant	Exon 2 of 2	ENST00000641002.1	NP_001004478.1	Q8NGY1A0A126GV63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10Z1	ENST00000641002.1 link	c.881A>C	p.Asn294Thr	missense_variant	Exon 2 of 2		NM_001004478.2	ENSP00000493003.1		Q8NGY1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34141

AN:

151976

Hom.:

4534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0920

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.272

AC:

68098

AN:

250596

Hom.:

10382

AF XY:

0.266

AC XY:

36063

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.0896

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.479

Gnomad SAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.258

AC:

376413

AN:

1461092

Hom.:

50979

Cov.:

AF XY:

0.254

AC XY:

184863

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.0838

Gnomad4 AMR exome

AF:

0.344

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.225

AC:

34171

AN:

152094

Hom.:

4538

Cov.:

AF XY:

0.230

AC XY:

17089

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0922

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.243

Gnomad4 EAS

AF:

0.493

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.329

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.245

Hom.:

7889

Bravo

AF:

0.223

TwinsUK

AF:

0.258

AC:

955

ALSPAC

AF:

0.249

AC:

958

ESP6500AA

AF:

0.0980

AC:

432

ESP6500EA

AF:

0.252

AC:

2170

ExAC

AF:

0.264

AC:

31992

Asia WGS

AF:

0.355

AC:

1232

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

.;D

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-4.9

.;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

1.0

D;D

Vest4

0.48

MPC

0.017

ClinPred

0.052

GERP RS

5.2

Varity_R

0.88

gMVP

0.15

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

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