11-124023236-C-T

Variant names:

• chr11-124023236-C-T
• rs1384751682
• NM_001001953.1:c.224C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001953.1(OR10G9):​c.224C>T​(p.Thr75Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,605,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: OR10G9 NM_001001953.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.304
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32380277).

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.224C>T	p.Thr75Met	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.224C>T	p.Thr75Met	missense	Exon 1 of 1	ENSP00000364164.1	Q8NGN4

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150724 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455258 Hom.: 0 Cov.: 35 AF XY: 0.00000415 AC XY: 3 AN XY: 723298

African (AFR) AF: 0.0000300 AC: 1 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5136

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1106934

Other (OTH) AF: 0.00 AC: 0 AN: 60094

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150724 Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1 AN XY: 73518

African (AFR) AF: 0.0000734 AC: 3 AN: 40872

American (AMR) AF: 0.00 AC: 0 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67722

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0081	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.30
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.52
MPC		1.0
ClinPred		0.98	D
GERP RS		3.3
PromoterAI		0.014	Neutral
Varity_R		0.33
gMVP		0.22
Mutation Taster		=96/4	polymorphism

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: rs1384751682; hg19: chr11-123893943;