NM_001001960.1:c.709G>A

Variant names:

• chr11-55913874-C-T
• rs773037389
• NM_001001960.1:c.709G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001960.1(OR5W2):​c.709G>A​(p.Ala237Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,610 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A237D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR5W2 NM_001001960.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 1 publications found

Genes affected

OR5W2 (HGNC:15299): (olfactory receptor family 5 subfamily W member 2) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22969645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001960.1. 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
	OR5W2	NM_001001960.1	MANE Select	c.709G>A	p.Ala237Thr	missense	Exon 1 of 1	NP_001001960.1	Q8NH69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5W2	ENST00000344514.1	TSL:6 MANE Select	c.709G>A	p.Ala237Thr	missense	Exon 1 of 1	ENSP00000342448.1	Q8NH69

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152138 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250784 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

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: 0.000164

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461610 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727118

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111772

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74458

African (AFR) AF: 0.00 AC: 0 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.15
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0055	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Benign	0.098	T
Sift4G	Benign	0.068	T
Polyphen		0.86	P
Vest4		0.18
MutPred		0.66		Gain of ubiquitination at K236 (P = 0.0719)
MVP		0.39
MPC		0.0072
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.16
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs773037389; hg19: chr11-55681350;