11-7927765-C-G

Position:

• chr11-7927765-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001004461.2(OR10A6):​c.898G>C​(p.Ala300Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR10A6 NM_001004461.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.175

Genes affected

OR10A6 (HGNC:15132): (olfactory receptor family 10 subfamily A member 6 (gene/pseudogene)) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10A6	NM_001004461.2	c.898G>C	p.Ala300Pro	missense_variant	4/4	ENST00000641238.1	NP_001004461.1
OR10A6	NM_001389574.1	c.898G>C	p.Ala300Pro	missense_variant	4/4		NP_001376503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10A6	ENST00000641238.1	c.898G>C	p.Ala300Pro	missense_variant	4/4		NM_001004461.2	ENSP00000493068.1
OR10A6	ENST00000642108.1	c.898G>C	p.Ala300Pro	missense_variant	4/4			ENSP00000492919.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.898G>C (p.A300P) alteration is located in exon 1 (coding exon 1) of the OR10A6 gene. This alteration results from a G to C substitution at nucleotide position 898, causing the alanine (A) at amino acid position 300 to be replaced by a proline (P). 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	0.34
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T;T;T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.44	N
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	4.1	H;H;H
PrimateAI	Benign	0.23	T
Polyphen		0.96	D;D;D
MutPred		0.76		Gain of glycosylation at A300 (P = 0.0065);Gain of glycosylation at A300 (P = 0.0065);Gain of glycosylation at A300 (P = 0.0065);
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.73
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs554206008; hg19: chr11-7949312;