11-4923405-A-T

Position:

chr11-4923405-A-T

Variant summary

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

The NM_001005237.1(OR51G1):c.935T>A(p.Ile312Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,571,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

OR51G1
NM_001005237.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

OR51G1 (HGNC:14738): (olfactory receptor family 51 subfamily G 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

OR51G1 links:

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

MMP26 links:

Genome browser will be placed here

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=0.07336947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51G1	NM_001005237.1 linkuse as main transcript	c.935T>A	p.Ile312Lys	missense_variant	1/1	ENST00000623849.1	NP_001005237.1	Q8NGK1A0A126GVF5
MMP26	NM_021801.5 linkuse as main transcript	c.-144-64663A>T		intron_variant		ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 linkuse as main transcript	c.-152-64865A>T		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR51G1	ENST00000623849.1 linkuse as main transcript	c.935T>A	p.Ile312Lys	missense_variant	1/1	6	NM_001005237.1	ENSP00000485612.1	Q8NGK1
MMP26	ENST00000380390.6 linkuse as main transcript	c.-144-64663A>T		intron_variant		5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 linkuse as main transcript	c.-152-64865A>T		intron_variant		1		ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000184

AC:

AN:

217922

Hom.:

AF XY:

0.0000259

AC XY:

AN XY:

115812

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000397

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1419616

Hom.:

Cov.:

AF XY:

0.0000257

AC XY:

AN XY:

701138

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:

0.0000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000392

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

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

Oct 01, 2024

The c.935T>A (p.I312K) alteration is located in exon 1 (coding exon 1) of the OR51G1 gene. This alteration results from a T to A substitution at nucleotide position 935, causing the isoleucine (I) at amino acid position 312 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

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.00066

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.17

M_CAP

Benign

0.0037

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.97

PrimateAI

Benign

0.29

Polyphen

0.0010

MutPred

0.62

Gain of disorder (P = 0.0108);

ClinPred

0.072

GERP RS

3.0

Varity_R

0.072

gMVP

0.19

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