Variant 14-18601202-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001013354.1(OR11H12):c.86T>C(p.Leu29Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000918 in 1,459,510 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000092 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

OR11H12
NM_001013354.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Variant links:

Genes affected

OR11H12 (HGNC:30738): (olfactory receptor family 11 subfamily H member 12) 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]

OR11H12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR11H12	NM_001013354.1 linkuse as main transcript	c.86T>C	p.Leu29Pro	missense_variant	1/1	ENST00000550708.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR11H12	ENST00000550708.2 linkuse as main transcript	c.86T>C	p.Leu29Pro	missense_variant	1/1		NM_001013354.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

149612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000680

AC:

AN:

249898

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000918

AC:

134

AN:

1459510

Hom.:

Cov.:

AF XY:

0.0000964

AC XY:

AN XY:

726070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000535

AC:

AN:

149612

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

72966

show subpopulations

Gnomad4 AFR

AF:

0.0000504

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000661

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

Sep 29, 2023

The c.86T>C (p.L29P) alteration is located in exon 1 (coding exon 1) of the OR11H12 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the leucine (L) at amino acid position 29 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

Benign

0.22

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.71

M_CAP

Benign

0.0049

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.6

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.069

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.68

MutPred

0.62

Gain of catalytic residue at N25 (P = 5e-04);

MVP

0.45

MPC

4.3

ClinPred

0.33

Varity_R

0.60

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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