chr10-45303854-T-A

Variant names:

• chr10-45303854-T-A
• rs577440539
• NM_001004297.3:c.569A>T

Variant summary

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

The NM_001004297.3(OR13A1):​c.569A>T​(p.Asn190Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N190S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR13A1 NM_001004297.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

OR13A1 (HGNC:14772): (olfactory receptor family 13 subfamily A 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004297.3. 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
	OR13A1	NM_001004297.3	MANE Select	c.569A>T	p.Asn190Ile	missense	Exon 4 of 4	NP_001004297.2	A0A126GVD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR13A1	ENST00000553795.6	TSL:6 MANE Select	c.569A>T	p.Asn190Ile	missense	Exon 4 of 4	ENSP00000451950.1	Q8NGR1
	OR13A1	ENST00000374401.3	TSL:6	c.569A>T	p.Asn190Ile	missense	Exon 4 of 4	ENSP00000363522.2	Q8NGR1
	OR13A1	ENST00000536058.1	TSL:6	c.569A>T	p.Asn190Ile	missense	Exon 3 of 3	ENSP00000438657.1	Q8NGR1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460470 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726600

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52008

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.48	N
M_CAP	Benign	0.0036	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		1.1
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.86	P
Vest4		0.61
MutPred		0.55		Loss of catalytic residue at N190 (P = 0.0831)
MVP		0.52
MPC		0.084
ClinPred		0.97	D
GERP RS		0.66
Varity_R		0.55
gMVP		0.16
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs577440539; hg19: chr10-45799302;