10-45303609-C-T

Variant names:

• chr10-45303609-C-T
• rs184948227
• NM_001004297.3:c.814G>A

Variant summary

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

The NM_001004297.3(OR13A1):​c.814G>A​(p.Ala272Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: OR13A1 NM_001004297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.377

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

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=0.034193724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR13A1	NM_001004297.3	c.814G>A	p.Ala272Thr	missense_variant	Exon 4 of 4	ENST00000553795.6	NP_001004297.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR13A1	ENST00000553795.6	c.814G>A	p.Ala272Thr	missense_variant	Exon 4 of 4	6	NM_001004297.3	ENSP00000451950.1
OR13A1	ENST00000374401.3	c.814G>A	p.Ala272Thr	missense_variant	Exon 4 of 4	6		ENSP00000363522.2
OR13A1	ENST00000536058.1	c.814G>A	p.Ala272Thr	missense_variant	Exon 3 of 3	6		ENSP00000438657.1

Frequencies

GnomAD3 genomes AF: 0.0000528 AC: 8 AN: 151554 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000319 AC: 8 AN: 250456 Hom.: 0 AF XY: 0.0000369 AC XY: 5 AN XY: 135416

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000150 AC: 22 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151672 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74176

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000491

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.814G>A (p.A272T) alteration is located in exon 4 (coding exon 1) of the OR13A1 gene. This alteration results from a G to A substitution at nucleotide position 814, causing the alanine (A) at amino acid position 272 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	0.14
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.29
DANN	Benign	0.57
DEOGEN2	Benign	0.00064	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.074	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.2	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	3.3	N;N;N
REVEL	Benign	0.049
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.056
MVP		0.13
MPC		0.021
ClinPred		0.035	T
GERP RS		2.9
Varity_R		0.030
gMVP		0.034

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: rs184948227; hg19: chr10-45799057; COSMIC: COSV65572166;