chr11-5947966-G-A

Variant names:

• chr11-5947966-G-A
• rs1414131062
• NM_001003443.3:c.620G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001003443.3(OR56A3):​c.620G>A​(p.Gly207Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G207V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: OR56A3 NM_001003443.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 1 publications found

Genes affected

OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) 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 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
OR56A3	NM_001003443.3	c.620G>A	p.Gly207Asp	missense_variant	Exon 3 of 3	ENST00000641160.1	NP_001003443.2
OR56A3	XM_047426926.1	c.620G>A	p.Gly207Asp	missense_variant	Exon 3 of 6		XP_047282882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR56A3	ENST00000641160.1	c.620G>A	p.Gly207Asp	missense_variant	Exon 3 of 3		NM_001003443.3	ENSP00000493059.1
OR56A3	ENST00000641905.1	c.620G>A	p.Gly207Asp	missense_variant	Exon 4 of 4			ENSP00000493319.1
OR56A3	ENST00000641878.1	n.402-721G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249748 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461840 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.013624), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.099
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.74	.;.;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.6	M;M;M
PhyloP100		-0.17
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.9	.;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.016	.;.;D
Sift4G	Uncertain	0.010	.;.;D
Polyphen		0.88	P;P;P
Vest4		0.18
MutPred		0.69		Loss of catalytic residue at W208 (P = 0.4042);Loss of catalytic residue at W208 (P = 0.4042);Loss of catalytic residue at W208 (P = 0.4042);
MVP		0.77
MPC		0.14
ClinPred		0.84	D
GERP RS		5.1
Varity_R		0.65
gMVP		0.72
Mutation Taster		=80/20	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: rs1414131062; hg19: chr11-5969196;