chr11-59365036-C-G

Position:

chr11-59365036-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004729.2(OR5AN1):c.578C>G(p.Thr193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,846 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

OR5AN1
NM_001004729.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.105

Variant links:

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]

OR5AN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13887587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5AN1	NM_001004729.2 linkuse as main transcript	c.578C>G	p.Thr193Ser	missense_variant	2/2	ENST00000641998.1	NP_001004729.1	Q8NGI8A0A126GVP9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR5AN1	ENST00000641998.1 linkuse as main transcript	c.578C>G	p.Thr193Ser	missense_variant	2/2		NM_001004729.2	ENSP00000493250.1	Q8NGI8
OR5AN1	ENST00000313940.2 linkuse as main transcript	c.578C>G	p.Thr193Ser	missense_variant	1/1	6		ENSP00000320302.2	Q8NGI8
OR5AN1	ENST00000641850.1 linkuse as main transcript	c.578C>G	p.Thr193Ser	missense_variant	2/2			ENSP00000492957.1	Q8NGI8

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251012

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

181

AN:

1461638

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727124

show subpopulations

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:

0.000158

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.578C>G (p.T193S) 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 578, causing the threonine (T) at amino acid position 193 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.019

T;T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.59

.;.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.6

.;.;D

REVEL

Benign

0.055

Sift

Benign

0.059

.;.;T

Sift4G

Benign

0.063

.;.;T

Polyphen

0.87

P;P;P

Vest4

0.11

MutPred

0.32

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.41

MPC

0.014

ClinPred

0.46

GERP RS

0.96

Varity_R

0.16

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over