Genetic Variant OR10A4:p.Pro263Ser (chr11-6877434-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_207186.2(OR10A4):c.787C>T(p.Pro263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

OR10A4
NM_207186.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Publications

1 publications found

Variant links:

Genes affected

OR10A4 (HGNC:15130): (olfactory receptor family 10 subfamily A member 4) 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]

OR10A4 links:

ENSG00000283415 (HGNC:):

ENSG00000283415 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207186.2. 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
	OR10A4	NM_207186.2	MANE Select	c.787C>T	p.Pro263Ser	missense	Exon 1 of 1	NP_997069.2	Q9H209

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR10A4	ENST00000379829.2	TSL:6 MANE Select	c.787C>T	p.Pro263Ser	missense	Exon 1 of 1	ENSP00000369157.2	Q9H209
ENSG00000283415	ENST00000637205.2	TSL:5	n.606-26616G>A		intron	N/A
ENSG00000283415	ENST00000767881.1		n.215-13134G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

250820

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.0000312

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

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

0.14

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.4

PhyloP100

2.2

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.14

Sift

Uncertain

0.019

Sift4G

Uncertain

0.021

Polyphen

0.98

Vest4

0.58

MutPred

0.56

Gain of phosphorylation at P263 (P = 0.0328)

MVP

0.56

MPC

0.029

ClinPred

0.65

GERP RS

4.0

Varity_R

0.22

gMVP

0.22

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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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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