Genetic Variant NM_001004059.3:c.14A>C (chr11-55650917-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004059.3(OR4S2):c.14A>C(p.Asn5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,255,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

OR4S2
NM_001004059.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.37

Publications

1 publications found

Variant links:

Genes affected

OR4S2 (HGNC:15183): (olfactory receptor family 4 subfamily S member 2) 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]

OR4S2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13714087).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4S2	NM_001004059.3	MANE Select	c.14A>C	p.Asn5Thr	missense	Exon 2 of 2	NP_001004059.2	A0A126GVG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4S2	ENST00000641692.1	MANE Select	c.14A>C	p.Asn5Thr	missense	Exon 2 of 2	ENSP00000493389.1	Q8NH73

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1255802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

627760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31382

American (AMR)

AF:

0.00

AC:

AN:

33740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23058

East Asian (EAS)

AF:

0.00

AC:

AN:

33952

South Asian (SAS)

AF:

0.00

AC:

AN:

75990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4404

European-Non Finnish (NFE)

AF:

0.00000210

AC:

AN:

953636

Other (OTH)

AF:

0.00

AC:

AN:

52336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.76

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.23

PhyloP100

-1.4

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.12

Sift

Benign

0.041

Sift4G

Benign

0.069

Polyphen

0.63

Vest4

0.060

MutPred

0.38

Loss of stability (P = 0.0759)

MVP

0.34

MPC

0.050

ClinPred

0.65

GERP RS

4.0

Varity_R

0.16

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over