11-4955129-T-A

Variant names:

• chr11-4955129-T-A
• rs747088187
• NM_001004748.1:c.585A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001004748.1(OR51A2):​c.585A>T​(p.Arg195Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,256,304 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000014 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR51A2 NM_001004748.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.28
• Publications: 1 publications found

Genes affected

OR51A2 (HGNC:14764): (olfactory receptor family 51 subfamily A member 2) 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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0816645).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004748.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51A2	NM_001004748.1	MANE Select	c.585A>T	p.Arg195Ser	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
	MMP26	NM_021801.5	MANE Select	c.-144-32939T>A		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-152-33141T>A		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51A2	ENST00000380371.1	TSL:6 MANE Select	c.585A>T	p.Arg195Ser	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-32939T>A		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-152-33141T>A		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 114074 Hom.: 0 Cov.: 17

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000461 AC: 1 AN: 216722 AF XY: 0.00000850

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.0000143 AC: 18 AN: 1256304 Hom.: 3 Cov.: 33 AF XY: 0.0000191 AC XY: 12 AN XY: 629112

African (AFR) AF: 0.00 AC: 0 AN: 31524

American (AMR) AF: 0.000411 AC: 15 AN: 36496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24016

East Asian (EAS) AF: 0.00 AC: 0 AN: 33968

South Asian (SAS) AF: 0.00 AC: 0 AN: 81302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5376

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 941726

Other (OTH) AF: 0.0000375 AC: 2 AN: 53324

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 114074 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 55242

African (AFR) AF: 0.00 AC: 0 AN: 34400

American (AMR) AF: 0.00 AC: 0 AN: 9994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2606

East Asian (EAS) AF: 0.00 AC: 0 AN: 3610

South Asian (SAS) AF: 0.00 AC: 0 AN: 3818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50462

Other (OTH) AF: 0.00 AC: 0 AN: 1470

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000893 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.070
DANN	Benign	0.77
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.52	N
PhyloP100		-6.3
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.029
Sift	Benign	0.098	T
Sift4G	Benign	0.19	T
Polyphen		0.057	B
Vest4		0.17
MutPred		0.56		Loss of stability (P = 0.1292)
MVP		0.65
MPC		1.4
ClinPred		0.10	T
GERP RS		-2.5
Varity_R		0.13
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs747088187; hg19: chr11-4976359;