NM_001001953.1:c.269C>T

Variant names:

• chr11-124023281-C-T
• rs11535718
• NM_001001953.1:c.269C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001953.1(OR10G9):​c.269C>T​(p.Ala90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,529,246 control chromosomes in the GnomAD database, including 55,335 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3368 hom., cov: 24)
  • Exomes 𝑓: 0.29 (51967 hom.)
• Consequence: OR10G9 NM_001001953.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.93
• Publications: 6 publications found

Genes affected

OR10G9 (HGNC:15129): (olfactory receptor family 10 subfamily G member 9) 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008943349).
• BP6: Variant 11-124023281-C-T is Benign according to our data. Variant chr11-124023281-C-T is described in ClinVar as Benign. ClinVar VariationId is 769812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001953.1. 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
	OR10G9	NM_001001953.1	MANE Select	c.269C>T	p.Ala90Val	missense	Exon 1 of 1	NP_001001953.1	Q8NGN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10G9	ENST00000375024.1	TSL:6 MANE Select	c.269C>T	p.Ala90Val	missense	Exon 1 of 1	ENSP00000364164.1	Q8NGN4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 32760 AN: 147190 Hom.: 3368 Cov.: 24

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.275 AC: 61267 AN: 222970 AF XY: 0.272

Gnomad AFR exome AF: 0.0628

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.338

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.290 AC: 400738 AN: 1381940 Hom.: 51967 Cov.: 32 AF XY: 0.288 AC XY: 197715 AN XY: 686438

African (AFR) AF: 0.0590 AC: 1936 AN: 32810

American (AMR) AF: 0.352 AC: 14951 AN: 42436

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6609 AN: 24766

East Asian (EAS) AF: 0.328 AC: 12751 AN: 38820

South Asian (SAS) AF: 0.237 AC: 19715 AN: 83312

European-Finnish (FIN) AF: 0.328 AC: 16990 AN: 51748

Middle Eastern (MID) AF: 0.152 AC: 704 AN: 4628

European-Non Finnish (NFE) AF: 0.297 AC: 310857 AN: 1045918

Other (OTH) AF: 0.282 AC: 16225 AN: 57502

GnomAD4 genome AF: 0.223 AC: 32778 AN: 147306 Hom.: 3368 Cov.: 24 AF XY: 0.226 AC XY: 16224 AN XY: 71694

African (AFR) AF: 0.0729 AC: 2967 AN: 40724

American (AMR) AF: 0.274 AC: 4006 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 869 AN: 3356

East Asian (EAS) AF: 0.332 AC: 1646 AN: 4954

South Asian (SAS) AF: 0.228 AC: 1039 AN: 4564

European-Finnish (FIN) AF: 0.311 AC: 3111 AN: 10004

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18412 AN: 65882

Other (OTH) AF: 0.214 AC: 436 AN: 2038

Alfa AF: 0.253 Hom.: 819

ExAC AF: 0.255 AC: 30488

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.9
DANN	Benign	0.51
DEOGEN2	Benign	0.00042	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.044	T
MetaRNN	Benign	0.0089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-2.9
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.038
Sift	Benign	0.42	T
Sift4G	Benign	0.58	T
Polyphen		0.011	B
Vest4		0.016
MPC		0.30
ClinPred		0.0021	T
GERP RS		0.22
PromoterAI		0.048	Neutral
Varity_R		0.036
gMVP		0.043
Mutation Taster		=100/0	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: rs11535718; hg19: chr11-123893988; COSMIC: COSV66685786; COSMIC: COSV66685786;