11-4488916-A-G

Position:

• chr11-4488916-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005171.3(OR52K1):​c.16A>G​(p.Ile6Val) 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 benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR52K1 NM_001005171.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.10

Genes affected

OR52K1 (HGNC:15222): (olfactory receptor family 52 subfamily K member 1) 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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02364844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52K1	NM_001005171.3	c.16A>G	p.Ile6Val	missense_variant	2/2	ENST00000641528.1	NP_001005171.2
OR52K1	NM_001385736.1	c.14-37A>G		intron_variant			NP_001372665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52K1	ENST00000641528.1	c.16A>G	p.Ile6Val	missense_variant	2/2		NM_001005171.3	ENSP00000493011	P1
	ENST00000690302.1	n.380-30747A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

Jan 16, 2024

The c.16A>G (p.I6V) alteration is located in exon 1 (coding exon 1) of the OR52K1 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the isoleucine (I) at amino acid position 6 to be replaced by a valine (V). 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	0.070
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.25
DEOGEN2	Benign	0.0021	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.015	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.12	.;N
REVEL	Benign	0.026
Sift	Benign	0.64	.;T
Sift4G	Benign	0.63	.;T
Polyphen		0.0	B;B
Vest4		0.067
MutPred		0.24		Gain of disorder (P = 0.1271);Gain of disorder (P = 0.1271);
MVP		0.095
ClinPred		0.053	T
GERP RS		-1.5
Varity_R		0.043
gMVP		0.085

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

Publications

LitVar

Other links and lift over

dbSNP: rs1846342153; hg19: chr11-4510146;