chr1-158607319-A-C

Variant names:

• chr1-158607319-A-C
• rs857685
• NM_001004478.2:c.881A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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.

• Frequency:
  • Genomes: 𝑓 0.22 (4538 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50979 hom.)
• Consequence: OR10Z1 NM_001004478.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• Publications: 31 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004478.2. 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
	OR10Z1	NM_001004478.2	MANE Select	c.881A>C	p.Asn294Thr	missense	Exon 2 of 2	NP_001004478.1	A0A126GV63

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10Z1	ENST00000641002.1	MANE Select	c.881A>C	p.Asn294Thr	missense	Exon 2 of 2	ENSP00000493003.1	Q8NGY1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34141 AN: 151976 Hom.: 4534 Cov.: 32

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

GnomAD2 exomes AF: 0.272 AC: 68098 AN: 250596 AF XY: 0.266

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 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.: 34 AF XY: 0.254 AC XY: 184863 AN XY: 726888

African (AFR) AF: 0.0838 AC: 2806 AN: 33466

American (AMR) AF: 0.344 AC: 15369 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 6111 AN: 26122

East Asian (EAS) AF: 0.439 AC: 17424 AN: 39692

South Asian (SAS) AF: 0.176 AC: 15187 AN: 86242

European-Finnish (FIN) AF: 0.338 AC: 18065 AN: 53394

Middle Eastern (MID) AF: 0.231 AC: 1331 AN: 5762

European-Non Finnish (NFE) AF: 0.256 AC: 284077 AN: 1111334

Other (OTH) AF: 0.266 AC: 16043 AN: 60372

GnomAD4 genome AF: 0.225 AC: 34171 AN: 152094 Hom.: 4538 Cov.: 32 AF XY: 0.230 AC XY: 17089 AN XY: 74342

African (AFR) AF: 0.0922 AC: 3830 AN: 41526

American (AMR) AF: 0.298 AC: 4557 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3466

East Asian (EAS) AF: 0.493 AC: 2535 AN: 5138

South Asian (SAS) AF: 0.180 AC: 869 AN: 4824

European-Finnish (FIN) AF: 0.329 AC: 3477 AN: 10582

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17176 AN: 67960

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.245 Hom.: 16538

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.8
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.48
MPC		0.017
ClinPred		0.052	T
GERP RS		5.2
Varity_R		0.88
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs857685; hg19: chr1-158577109; COSMIC: COSV63525192; COSMIC: COSV63525192;