11-59422866-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001001954.2(OR5A2):c.88A>G(p.Met30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,872 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: OR5A2 NM_001001954.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.74

Genes affected

OR5A2 (HGNC:15249): (olfactory receptor family 5 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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.013813049).
• BP6: Variant 11-59422866-T-C is Benign according to our data. Variant chr11-59422866-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3206084.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5A2	NM_001001954.2	c.88A>G	p.Met30Val	missense_variant	2/2	ENST00000302040.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5A2	ENST00000302040.6	c.88A>G	p.Met30Val	missense_variant	2/2		NM_001001954.2	P1
OR5A2	ENST00000641361.1	c.88A>G	p.Met30Val	missense_variant	2/2			P1
OR5A2	ENST00000641673.1	c.88A>G	p.Met30Val	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000318 AC: 8 AN: 251280 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461872 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0030
Dann	Benign	0.15
DEOGEN2	Benign	0.0039	T;T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0031	N
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.014	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.3	N;N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.98	N;.;.
REVEL	Benign	0.024
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;.;.
Polyphen		0.0	B;B;B
Vest4		0.035
MutPred		0.20		Gain of catalytic residue at M30 (P = 0.064);Gain of catalytic residue at M30 (P = 0.064);Gain of catalytic residue at M30 (P = 0.064);
MVP		0.061
MPC		0.026
ClinPred		0.031	T
GERP RS		-1.4
Varity_R		0.047
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs370752643; hg19: chr11-59190339;