Variant 6-29307045-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030946.2(OR14J1):c.356A>G(p.Asp119Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,460,764 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: 0.000015 ( 0 hom. )

Consequence

OR14J1
NM_030946.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

Variant links:

Genes affected

OR14J1 (HGNC:13971): (olfactory receptor family 14 subfamily J 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]

OR14J1 links:

LOC105375005 (HGNC:):

LOC105375005 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR14J1	NM_030946.2 linkuse as main transcript	c.356A>G	p.Asp119Gly	missense_variant	2/2	ENST00000641895.1	NP_112208.1
LOC105375005	XR_926670.1 linkuse as main transcript	n.220-22085T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR14J1	ENST00000641895.1 linkuse as main transcript	c.356A>G	p.Asp119Gly	missense_variant	2/2		NM_030946.2	ENSP00000492893	P1
OR14J1	ENST00000377160.4 linkuse as main transcript	c.356A>G	p.Asp119Gly	missense_variant	1/1			ENSP00000366365	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000446

AC:

AN:

246696

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134406

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 SAS exome

AF:

0.000362

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1460764

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726694

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:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000677

AC:

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

Aug 12, 2021

The c.356A>G (p.D119G) alteration is located in exon 1 (coding exon 1) of the OR14J1 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the aspartic acid (D) at amino acid position 119 to be replaced by a glycine (G). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.0026

MetaRNN

Pathogenic

0.90

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.6

H;H

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-6.9

.;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.0020

.;D

Polyphen

1.0

D;D

Vest4

0.74

MutPred

0.82

Gain of methylation at R120 (P = 0.089);Gain of methylation at R120 (P = 0.089);

MVP

0.40

MPC

0.32

ClinPred

0.89

GERP RS

3.7

Varity_R

0.73

gMVP

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over