Genetic Variant NM_001001921.2:c.290G>A (chr11-56030708-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001001921.2(OR5AS1):c.290G>A(p.Cys97Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. C97S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OR5AS1
NM_001001921.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.67

Publications

0 publications found

Variant links:

Genes affected

OR5AS1 (HGNC:15261): (olfactory receptor family 5 subfamily AS 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]

OR5AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5AS1	NM_001001921.2 link	c.290G>A	p.Cys97Tyr	missense_variant	Exon 2 of 2	ENST00000641320.1	NP_001001921.1	Q8N127A0A126GVD4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5AS1	ENST00000641320.1 link	c.290G>A	p.Cys97Tyr	missense_variant	Exon 2 of 2		NM_001001921.2	ENSP00000493325.1		Q8N127

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33322

American (AMR)

AF:

0.00

AC:

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.00

AC:

AN:

85900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109148

Other (OTH)

AF:

0.0000166

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.088

T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.0026

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

H;H

PhyloP100

7.7

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-10

.;D

REVEL

Benign

0.23

Sift

Uncertain

0.0090

.;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

0.99

D;D

Vest4

0.65

MutPred

0.69

Gain of disorder (P = 0.0893);Gain of disorder (P = 0.0893);

MVP

0.63

MPC

0.0099

ClinPred

1.0

GERP RS

5.5

Varity_R

0.75

gMVP

0.47

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.34

Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over