Variant 6-29307627-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030946.2(OR14J1):c.938T>A(p.Met313Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000749 in 1,601,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

OR14J1
NM_030946.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037035525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR14J1	NM_030946.2 linkuse as main transcript	c.938T>A	p.Met313Lys	missense_variant	2/2	ENST00000641895.1	NP_112208.1	Q9UGF5A0A126GW10
LOC105375005	XR_926670.1 linkuse as main transcript	n.220-22667A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR14J1	ENST00000641895.1 linkuse as main transcript	c.938T>A	p.Met313Lys	missense_variant	2/2		NM_030946.2	ENSP00000492893.1		Q9UGF5
OR14J1	ENST00000377160.4 linkuse as main transcript	c.938T>A	p.Met313Lys	missense_variant	1/1	6		ENSP00000366365.2		Q9UGF5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000845

AC:

AN:

236572

Hom.:

AF XY:

0.00000771

AC XY:

AN XY:

129632

show subpopulations

Gnomad AFR exome

AF:

0.000137

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1449216

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.0000453

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000171

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

May 20, 2024

The c.938T>A (p.M313K) alteration is located in exon 1 (coding exon 1) of the OR14J1 gene. This alteration results from a T to A substitution at nucleotide position 938, causing the methionine (M) at amino acid position 313 to be replaced by a lysine (K). 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

0.089

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.3

DANN

Benign

0.76

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.097

M_CAP

Benign

0.0031

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.20

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.55

.;N

REVEL

Benign

0.011

Sift

Benign

0.15

.;T

Sift4G

Benign

0.24

.;T

Polyphen

0.023

B;B

Vest4

0.45

MVP

0.048

MPC

0.31

ClinPred

0.022

GERP RS

1.9

Varity_R

0.31

gMVP

0.31

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

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