Variant chr6-29307053-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030946.2(OR14J1):c.364G>C(p.Ala122Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR14J1
NM_030946.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0770

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22674277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR14J1	NM_030946.2 link	c.364G>C	p.Ala122Pro	missense_variant	2/2	ENST00000641895.1	NP_112208.1	Q9UGF5A0A126GW10
LOC105375005	XR_926670.1 link	n.220-22093C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR14J1	ENST00000641895.1 link	c.364G>C	p.Ala122Pro	missense_variant	2/2		NM_030946.2	ENSP00000492893.1		Q9UGF5
OR14J1	ENST00000377160.4 link	c.364G>C	p.Ala122Pro	missense_variant	1/1	6		ENSP00000366365.2		Q9UGF5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726660

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:

8.99e-7

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

Oct 09, 2024

The c.364G>C (p.A122P) alteration is located in exon 1 (coding exon 1) of the OR14J1 gene. This alteration results from a G to C substitution at nucleotide position 364, causing the alanine (A) at amino acid position 122 to be replaced by a proline (P). 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

Pathogenic

0.67

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.0041

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.11

Sift

Uncertain

0.0030

.;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

0.88

P;P

Vest4

0.39

MutPred

0.57

Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);

MVP

0.14

MPC

0.54

ClinPred

0.83

GERP RS

0.092

Varity_R

0.41

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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