11-5948159-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003443.3(OR56A3):c.813A>T(p.Lys271Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,614,082 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

OR56A3
NM_001003443.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.06

Publications

6 publications found

Variant links:

Genes affected

OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) 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]

OR56A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03150797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR56A3	NM_001003443.3 link	c.813A>T	p.Lys271Asn	missense_variant	Exon 3 of 3	ENST00000641160.1	NP_001003443.2	Q8NH54A0A126GWL6
OR56A3	XM_047426926.1 link	c.813A>T	p.Lys271Asn	missense_variant	Exon 3 of 6		XP_047282882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR56A3	ENST00000641160.1 link	c.813A>T	p.Lys271Asn	missense_variant	Exon 3 of 3	NM_001003443.3	ENSP00000493059.1	Q8NH54
OR56A3	ENST00000641905.1 link	c.813A>T	p.Lys271Asn	missense_variant	Exon 4 of 4		ENSP00000493319.1	Q8NH54
OR56A3	ENST00000641878.1 link	n.402-528A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000544

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000240

AC:

AN:

249754

AF XY:

0.000251

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000467

AC:

683

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

310

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000577

AC:

642

AN:

1112002

Other (OTH)

AF:

0.000546

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000322

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41452

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68036

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.813A>T (p.K271N) alteration is located in exon 1 (coding exon 1) of the OR56A3 gene. This alteration results from a A to T substitution at nucleotide position 813, causing the lysine (K) at amino acid position 271 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

0.15

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.043

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.37

.;.;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.28

N;N;N

PhyloP100

-3.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

.;.;N

REVEL

Benign

0.051

Sift

Benign

0.38

.;.;T

Sift4G

Benign

0.48

.;.;T

Polyphen

0.0030

B;B;B

Vest4

0.10

MutPred

0.35

Loss of methylation at K271 (P = 0.0069);Loss of methylation at K271 (P = 0.0069);Loss of methylation at K271 (P = 0.0069);

MVP

0.17

MPC

0.10

ClinPred

0.027

GERP RS

-5.5

Varity_R

0.11

gMVP

0.12

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

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11-5948159-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over