Variant 14-18601123-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013354.1(OR11H12):c.7C>A(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000078 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000053 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR11H12
NM_001013354.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.031958073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR11H12	NM_001013354.1 linkuse as main transcript	c.7C>A	p.Pro3Thr	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.7C>A	p.Pro3Thr	missense_variant	1/1		NM_001013354.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000784

AC:

AN:

140264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000716

Gnomad ASJ

AF:

0.000302

Gnomad EAS

AF:

0.000213

Gnomad SAS

AF:

0.000233

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000619

Gnomad OTH

AF:

0.000532

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

103418

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

53092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000412

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000102

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000533

AC:

AN:

1389486

Hom.:

Cov.:

AF XY:

0.0000503

AC XY:

AN XY:

695366

show subpopulations

Gnomad4 AFR exome

AF:

0.0000649

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.000312

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000372

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000784

AC:

AN:

140368

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

68114

show subpopulations

Gnomad4 AFR

AF:

0.0000549

Gnomad4 AMR

AF:

0.0000715

Gnomad4 ASJ

AF:

0.000302

Gnomad4 EAS

AF:

0.000213

Gnomad4 SAS

AF:

0.000233

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000619

Gnomad4 OTH

AF:

0.000528

Alfa

AF:

0.0000961

Hom.:

ExAC

AF:

0.0000377

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 10, 2024

The c.7C>A (p.P3T) alteration is located in exon 1 (coding exon 1) of the OR11H12 gene. This alteration results from a C to A substitution at nucleotide position 7, causing the proline (P) at amino acid position 3 to be replaced by a threonine (T). 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

0.072

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.5

DANN

Benign

0.44

DEOGEN2

Benign

0.00022

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.31

M_CAP

Benign

0.0081

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.45

PROVEAN

Benign

0.18

REVEL

Benign

0.033

Sift

Benign

0.44

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.11

MutPred

0.35

Gain of catalytic residue at V8 (P = 0);

MVP

0.35

MPC

1.8

ClinPred

0.027

Varity_R

0.035

gMVP

0.058

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