11-4907977-C-T

Variant names:

• chr11-4907977-C-T
• rs531013617
• NM_001004749.2:c.608C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004749.2(OR51A7):​c.608C>T​(p.Ala203Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: OR51A7 NM_001004749.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0830

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]

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

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=0.11105463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A7	NM_001004749.2	c.608C>T	p.Ala203Val	missense_variant	Exon 2 of 2	ENST00000641490.1	NP_001004749.1
MMP26	NM_021801.5	c.-144-80091C>T		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-152-80293C>T		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51A7	ENST00000641490.1	c.608C>T	p.Ala203Val	missense_variant	Exon 2 of 2		NM_001004749.2	ENSP00000493162.1
MMP26	ENST00000380390.6	c.-144-80091C>T		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-152-80293C>T		intron_variant	Intron 2 of 7	1		ENSP00000300762.2
OR51A7	ENST00000359350.5	c.608C>T	p.Ala203Val	missense_variant	Exon 1 of 1	6		ENSP00000352305.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251218 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135776

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: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461808 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727210

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: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.608C>T (p.A203V) alteration is located in exon 1 (coding exon 1) of the OR51A7 gene. This alteration results from a C to T substitution at nucleotide position 608, causing the alanine (A) at amino acid position 203 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0016	T;T
Eigen	Benign	0.0080
Eigen_PC	Benign	-0.0030
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.26	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.61	.;N
REVEL	Benign	0.27
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	.;T
Polyphen		0.85	P;P
Vest4		0.082
MutPred		0.49		Gain of helix (P = 0.5668);Gain of helix (P = 0.5668);
MVP		0.69
MPC		0.013
ClinPred		0.15	T
GERP RS		5.0
Varity_R		0.047
gMVP		0.092

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

Other links and lift over

dbSNP: rs531013617; hg19: chr11-4929207;