11-124023178-C-A

Variant names:

• chr11-124023178-C-A
• rs756703887
• NM_001001953.1:c.166C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001953.1(OR10G9):​c.166C>A​(p.Pro56Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: OR10G9 NM_001001953.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10G9	NM_001001953.1	c.166C>A	p.Pro56Thr	missense_variant	Exon 1 of 1	ENST00000375024.1	NP_001001953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10G9	ENST00000375024.1	c.166C>A	p.Pro56Thr	missense_variant	Exon 1 of 1	6	NM_001001953.1	ENSP00000364164.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD3 exomes AF: 0.0000480 AC: 12 AN: 250224 Hom.: 0 AF XY: 0.0000296 AC XY: 4 AN XY: 135188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1461500 Hom.: 0 Cov.: 36 AF XY: 0.0000165 AC XY: 12 AN XY: 727056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 29

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166C>A (p.P56T) alteration is located in exon 1 (coding exon 1) of the OR10G9 gene. This alteration results from a C to A substitution at nucleotide position 166, causing the proline (P) at amino acid position 56 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0021	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.3	H
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.035	B
Vest4		0.76
MVP		0.52
MPC		0.37
ClinPred		0.39	T
GERP RS		3.3
Varity_R		0.79
gMVP		0.14

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

Other links and lift over

dbSNP: rs756703887; hg19: chr11-123893885;