11-4923425-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005237.1(OR51G1):c.915C>G(p.Ile305Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,593,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR51G1
NM_001005237.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.468

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11472419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51G1	NM_001005237.1 link	c.915C>G	p.Ile305Met	missense_variant	Exon 1 of 1	ENST00000623849.1	NP_001005237.1	Q8NGK1A0A126GVF5
MMP26	NM_021801.5 link	c.-144-64643G>C		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 link	c.-152-64845G>C		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR51G1	ENST00000623849.1 link	c.915C>G	p.Ile305Met	missense_variant	Exon 1 of 1	6	NM_001005237.1	ENSP00000485612.1	Q8NGK1
MMP26	ENST00000380390.6 link	c.-144-64643G>C		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 link	c.-152-64845G>C		intron_variant	Intron 2 of 7	1		ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1441320

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32850

American (AMR)

AF:

0.0000234

AC:

AN:

42780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24694

East Asian (EAS)

AF:

0.00

AC:

AN:

39444

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1100844

Other (OTH)

AF:

0.00

AC:

AN:

59476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.915C>G (p.I305M) alteration is located in exon 1 (coding exon 1) of the OR51G1 gene. This alteration results from a C to G substitution at nucleotide position 915, causing the isoleucine (I) at amino acid position 305 to be replaced by a methionine (M). 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

0.095

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.23

M_CAP

Benign

0.0074

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.70

PrimateAI

Benign

0.37

Polyphen

0.58

MutPred

0.52

Gain of methylation at K307 (P = 0.1245);

ClinPred

0.33

GERP RS

-3.4

Varity_R

0.049

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

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.

11-4923425-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over