11-59365219-C-G

Position:

• chr11-59365219-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004729.2(OR5AN1):​c.761C>G​(p.Thr254Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: OR5AN1 NM_001004729.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.02

Genes affected

OR5AN1 (HGNC:15255): (olfactory receptor family 5 subfamily AN 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5AN1	NM_001004729.2	c.761C>G	p.Thr254Arg	missense_variant	2/2	ENST00000641998.1	NP_001004729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5AN1	ENST00000641998.1	c.761C>G	p.Thr254Arg	missense_variant	2/2		NM_001004729.2	ENSP00000493250.1
OR5AN1	ENST00000313940.2	c.761C>G	p.Thr254Arg	missense_variant	1/1	6		ENSP00000320302.2
OR5AN1	ENST00000641850.1	c.761C>G	p.Thr254Arg	missense_variant	2/2			ENSP00000492957.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Nov 24, 2024

The c.761C>G (p.T254R) alteration is located in exon 1 (coding exon 1) of the OR5AN1 gene. This alteration results from a C to G substitution at nucleotide position 761, causing the threonine (T) at amino acid position 254 to be replaced by an arginine (R). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	T;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.55	.;.;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.85	.;.;N
REVEL	Benign	0.11
Sift	Uncertain	0.0010	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		0.96	D;D;D
Vest4		0.29
MutPred		0.68		Loss of glycosylation at S255 (P = 0.0708);Loss of glycosylation at S255 (P = 0.0708);Loss of glycosylation at S255 (P = 0.0708);
MVP		0.38
MPC		0.0076
ClinPred		0.48	T
GERP RS		0.083
Varity_R		0.39
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.48		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1386702401; hg19: chr11-59132692;