11-58507862-C-T

Position:

• chr11-58507862-C-T

Variant summary

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

The NM_001005218.3(OR5B21):​c.244G>A​(p.Ala82Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR5B21 NM_001005218.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.315

Genes affected

OR5B21 (HGNC:19616): (olfactory receptor family 5 subfamily B member 21) 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]

LOC105369313 (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=0.051858008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5B21	NM_001005218.3	c.244G>A	p.Ala82Thr	missense_variant	1/1	ENST00000360374.3	NP_001005218.1
LOC105369313	XR_007062673.1	n.239-2320G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5B21	ENST00000360374.3	c.244G>A	p.Ala82Thr	missense_variant	1/1	6	NM_001005218.3	ENSP00000353537.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250874 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135562

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Dec 03, 2024

The c.244G>A (p.A82T) alteration is located in exon 1 (coding exon 1) of the OR5B21 gene. This alteration results from a G to A substitution at nucleotide position 244, causing the alanine (A) at amino acid position 82 to be replaced by a threonine (T). 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	0.087
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.060	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.48	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.081
Sift	Uncertain	0.024	D
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.48		Gain of glycosylation at A82 (P = 0.0665);
MVP		0.072
MPC		0.025
ClinPred		0.070	T
GERP RS		3.0
Varity_R		0.14
gMVP		0.054

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: rs1382922532; hg19: chr11-58275335;