10-45303557-C-T

Variant names:

• chr10-45303557-C-T
• rs375578619
• NM_001004297.3:c.866G>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.866G>A​(p.Ser289Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: OR13A1 NM_001004297.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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=0.024011254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR13A1	NM_001004297.3	c.866G>A	p.Ser289Asn	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.866G>A	p.Ser289Asn	missense_variant	Exon 4 of 4	6	NM_001004297.3	ENSP00000451950.1
OR13A1	ENST00000374401.3	c.866G>A	p.Ser289Asn	missense_variant	Exon 4 of 4	6		ENSP00000363522.2
OR13A1	ENST00000536058.1	c.866G>A	p.Ser289Asn	missense_variant	Exon 3 of 3	6		ENSP00000438657.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000144 AC: 36 AN: 250650 Hom.: 0 AF XY: 0.000170 AC XY: 23 AN XY: 135562

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000568 AC: 83 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47 AN XY: 727206

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74478

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.0000680

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000123 AC: 15

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.866G>A (p.S289N) 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 866, causing the serine (S) at amino acid position 289 to be replaced by an asparagine (N). 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	0.16
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00039	T;T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.079	N
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.024	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.67	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.48	N;N;N
REVEL	Benign	0.078
Sift	Benign	0.033	D;D;D
Sift4G	Benign	0.090	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.17
MVP		0.16
MPC		0.022
ClinPred		0.035	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.088

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: rs375578619; hg19: chr10-45799005;