Variant chr15-22095046-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001005241.4(OR4N4):c.525C>A(p.Asp175Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 8)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR4N4
NM_001005241.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

OR4N4 (HGNC:15375): (olfactory receptor family 4 subfamily N 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]

OR4N4 links:

OR4M2-OT1 (HGNC:):

OR4M2-OT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR4N4	NM_001005241.4 linkuse as main transcript	c.525C>A	p.Asp175Glu	missense_variant	1/1	ENST00000328795.6
OR4M2-OT1	NR_110480.1 linkuse as main transcript	n.1102+255C>A		intron_variant, non_coding_transcript_variant
OR4M2-OT1	NR_110481.1 linkuse as main transcript	n.834+255C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4N4	ENST00000328795.6 linkuse as main transcript	c.525C>A	p.Asp175Glu	missense_variant	1/1		NM_001005241.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000126

AC:

AN:

796242

Hom.:

Cov.:

AF XY:

0.00000247

AC XY:

AN XY:

404552

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:

0.00000174

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 21, 2023

The c.525C>A (p.D175E) alteration is located in exon 1 (coding exon 1) of the OR4N4 gene. This alteration results from a C to A substitution at nucleotide position 525, causing the aspartic acid (D) at amino acid position 175 to be replaced by a glutamic acid (E). 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

0.32

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0067

.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.77

T;.

M_CAP

Benign

0.0032

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.9

.;D

REVEL

Benign

0.086

Sift

Uncertain

0.0070

.;D

Sift4G

Uncertain

0.0050

.;D

Polyphen

0.91

.;P

Vest4

0.062

MutPred

0.75

Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);

MVP

0.27

MPC

0.40

ClinPred

0.98

GERP RS

-0.47

Varity_R

0.69

gMVP

0.093

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over