dbSNP rs377602088: OR51A7:p.Ala149Asp (chr11-4907815-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001004749.2(OR51A7):c.446C>A(p.Ala149Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A149G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR51A7
NM_001004749.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.234

Variant links:

Genes affected

OR51A7 (HGNC:15188): (olfactory receptor family 51 subfamily A member 7) 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]

OR51A7 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 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=0.20247728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A7	NM_001004749.2 link	c.446C>A	p.Ala149Asp	missense_variant	Exon 2 of 2	ENST00000641490.1	NP_001004749.1	Q8NH64
MMP26	NM_021801.5 link	c.-144-80253C>A		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 link	c.-152-80455C>A		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR51A7	ENST00000641490.1 link	c.446C>A	p.Ala149Asp	missense_variant	Exon 2 of 2		NM_001004749.2	ENSP00000493162.1	Q8NH64
MMP26	ENST00000380390.6 link	c.-144-80253C>A		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 link	c.-152-80455C>A		intron_variant	Intron 2 of 7	1		ENSP00000300762.2	A0A8J8YUH5
OR51A7	ENST00000359350.5 link	c.446C>A	p.Ala149Asp	missense_variant	Exon 1 of 1	6		ENSP00000352305.4	Q8NH64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250620

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135426

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727116

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

0.079

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.063

.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.2

.;D

REVEL

Uncertain

0.44

Sift

Benign

0.042

.;D

Sift4G

Uncertain

0.038

.;D

Polyphen

0.87

P;P

Vest4

0.57

MutPred

0.45

Loss of MoRF binding (P = 0.0657);Loss of MoRF binding (P = 0.0657);

MVP

0.73

MPC

0.0081

ClinPred

0.62

GERP RS

5.0

Varity_R

0.60

gMVP

0.78

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over