NM_001005188.1:c.569C>A

Variant names:

• chr11-123753950-G-T
• rs12364099
• NM_001005188.1:c.569C>A

Variant summary

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

The NM_001005188.1(OR6X1):​c.569C>A​(p.Thr190Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,614,032 control chromosomes in the GnomAD database, including 17,430 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.11 (1253 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16177 hom.)
• Consequence: OR6X1 NM_001005188.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 18 publications found

Genes affected

OR6X1 (HGNC:14737): (olfactory receptor family 6 subfamily X 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=0.0013703108).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005188.1. 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
	OR6X1	NM_001005188.1	MANE Select	c.569C>A	p.Thr190Asn	missense	Exon 1 of 1	NP_001005188.1	A0A126GVM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6X1	ENST00000327930.3	TSL:6 MANE Select	c.569C>A	p.Thr190Asn	missense	Exon 1 of 1	ENSP00000333724.2	Q8NH79

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17038 AN: 152092 Hom.: 1256 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.123 AC: 30855 AN: 251380 AF XY: 0.127

Gnomad AFR exome AF: 0.0325

Gnomad AMR exome AF: 0.0749

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.0245

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.143 AC: 209595 AN: 1461822 Hom.: 16177 Cov.: 34 AF XY: 0.144 AC XY: 104404 AN XY: 727210

African (AFR) AF: 0.0353 AC: 1182 AN: 33480

American (AMR) AF: 0.0800 AC: 3579 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 6178 AN: 26136

East Asian (EAS) AF: 0.0198 AC: 786 AN: 39700

South Asian (SAS) AF: 0.103 AC: 8850 AN: 86258

European-Finnish (FIN) AF: 0.143 AC: 7638 AN: 53418

Middle Eastern (MID) AF: 0.208 AC: 1198 AN: 5768

European-Non Finnish (NFE) AF: 0.154 AC: 171564 AN: 1111944

Other (OTH) AF: 0.143 AC: 8620 AN: 60394

GnomAD4 genome AF: 0.112 AC: 17032 AN: 152210 Hom.: 1253 Cov.: 32 AF XY: 0.110 AC XY: 8215 AN XY: 74408

African (AFR) AF: 0.0371 AC: 1540 AN: 41556

American (AMR) AF: 0.101 AC: 1538 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5178

South Asian (SAS) AF: 0.0966 AC: 465 AN: 4814

European-Finnish (FIN) AF: 0.144 AC: 1528 AN: 10596

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10550 AN: 67994

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.143 Hom.: 7748

Bravo AF: 0.105

TwinsUK AF: 0.151 AC: 559

ALSPAC AF: 0.168 AC: 646

ESP6500AA AF: 0.0425 AC: 187

ESP6500EA AF: 0.156 AC: 1342

ExAC AF: 0.122 AC: 14797

Asia WGS AF: 0.0560 AC: 194 AN: 3478

EpiCase AF: 0.163

EpiControl AF: 0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.7
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.10
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		0.029	B
Vest4		0.081
MPC		0.15
ClinPred		0.073	T
GERP RS		3.5
Varity_R		0.63
gMVP		0.25
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12364099; hg19: chr11-123624658; COSMIC: COSV99080043;