11-7927779-C-T

Position:

• chr11-7927779-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004461.2(OR10A6):​c.884G>A​(p.Ser295Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,960 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: OR10A6 NM_001004461.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.657

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076756477).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10A6	NM_001004461.2	c.884G>A	p.Ser295Asn	missense_variant	4/4	ENST00000641238.1	NP_001004461.1
OR10A6	NM_001389574.1	c.884G>A	p.Ser295Asn	missense_variant	4/4		NP_001376503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10A6	ENST00000641238.1	c.884G>A	p.Ser295Asn	missense_variant	4/4		NM_001004461.2	ENSP00000493068.1
OR10A6	ENST00000642108.1	c.884G>A	p.Ser295Asn	missense_variant	4/4			ENSP00000492919.1

Frequencies

GnomAD3 genomes AF: 0.000887 AC: 135 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000754 AC: 189 AN: 250796 Hom.: 0 AF XY: 0.000686 AC XY: 93 AN XY: 135538

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000832

Gnomad NFE exome AF: 0.00124

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00147 AC: 2146 AN: 1461644 Hom.: 3 Cov.: 30 AF XY: 0.00139 AC XY: 1011 AN XY: 727122

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000674

Gnomad4 NFE exome AF: 0.00180

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.000886 AC: 135 AN: 152316 Hom.: 0 Cov.: 33 AF XY: 0.000806 AC XY: 60 AN XY: 74478

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00134 Hom.: 1

Bravo AF: 0.000835

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000610 AC: 74

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00119

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

Oct 22, 2021

The c.884G>A (p.S295N) alteration is located in exon 1 (coding exon 1) of the OR10A6 gene. This alteration results from a G to A substitution at nucleotide position 884, causing the serine (S) at amino acid position 295 to be replaced by an asparagine (N). 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	Benign	0.092
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.73
DEOGEN2	Benign	0.00044	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.025	N;N;N
PrimateAI	Benign	0.19	T
Polyphen		0.0030	B;B;B
ClinPred		0.0025	T
GERP RS		-2.8
Varity_R		0.044
gMVP		0.074

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

Publications

LitVar

Other links and lift over

dbSNP: rs138423664; hg19: chr11-7949326; COSMIC: COSV59165407;