NM_001001921.2:c.244C>A

Variant names:

• chr11-56030662-C-A
• rs1407948551
• NM_001001921.2:c.244C>A

Variant summary

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

The NM_001001921.2(OR5AS1):​c.244C>A​(p.Leu82Met) 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. 14/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR5AS1 NM_001001921.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.110
• Publications: 0 publications found

Genes affected

OR5AS1 (HGNC:15261): (olfactory receptor family 5 subfamily AS 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

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=0.24611631).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001921.2. 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
	OR5AS1	NM_001001921.2	MANE Select	c.244C>A	p.Leu82Met	missense	Exon 2 of 2	NP_001001921.1	A0A126GVD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5AS1	ENST00000641320.1	MANE Select	c.244C>A	p.Leu82Met	missense	Exon 2 of 2	ENSP00000493325.1	Q8N127

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1430250 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 707852

African (AFR) AF: 0.00 AC: 0 AN: 32532

American (AMR) AF: 0.00 AC: 0 AN: 41348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23814

East Asian (EAS) AF: 0.00 AC: 0 AN: 39334

South Asian (SAS) AF: 0.00 AC: 0 AN: 81634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095072

Other (OTH) AF: 0.00 AC: 0 AN: 58904

GnomAD4 genome Cov.: 32

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	0.23
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		-0.11
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.16
Sift	Benign	0.094	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.57		Loss of catalytic residue at L82 (P = 0.0495)
MVP		0.30
MPC		0.0071
ClinPred		0.40	T
GERP RS		2.6
Varity_R		0.19
gMVP		0.052
Mutation Taster		=83/17	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: rs1407948551; hg19: chr11-55798138;