11-4449476-C-G

Variant names:

• chr11-4449476-C-G
• rs780957977
• NM_001005172.2:c.137C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005172.2(OR52K2):​c.137C>G​(p.Thr46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. T46I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR52K2 NM_001005172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• Publications: 1 publications found

Genes affected

OR52K2 (HGNC:15223): (olfactory receptor family 52 subfamily K 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]

ENSG00000291144 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044798076).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005172.2. 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
	OR52K2	NM_001005172.2	MANE Select	c.137C>G	p.Thr46Ser	missense	Exon 1 of 1	NP_001005172.2	Q8NGK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52K2	ENST00000325719.4	TSL:6 MANE Select	c.137C>G	p.Thr46Ser	missense	Exon 1 of 1	ENSP00000318956.4	Q8NGK3
	ENSG00000291144	ENST00000641797.5		n.387-19891C>G		intron	N/A
	ENSG00000291144	ENST00000685350.2		n.392-19891C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000812 AC: 2 AN: 246448 AF XY: 0.0000150

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: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456896 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724492

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25622

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 85436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109298

Other (OTH) AF: 0.00 AC: 0 AN: 60182

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.9
DANN	Benign	0.93
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.92	L
PhyloP100		0.79
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.038
Sift	Benign	0.19	T
Sift4G	Benign	0.17	T
Polyphen		0.043	B
Vest4		0.079
MutPred		0.52		Loss of sheet (P = 0.1158)
MVP		0.20
MPC		0.0039
ClinPred		0.047	T
GERP RS		3.4
PromoterAI		-0.015	Neutral
Varity_R		0.13
gMVP		0.17
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: rs780957977; hg19: chr11-4470706;