11-55811641-A-G

Variant names:

• chr11-55811641-A-G
• rs377702509
• NM_001004738.2:c.175A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004738.2(OR5L1):​c.175A>G​(p.Met59Val) variant causes a missense change. The variant allele was found at a frequency of 0.000182 in 1,613,772 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (3 hom.)
• Consequence: OR5L1 NM_001004738.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86

Genes affected

OR5L1 (HGNC:8350): (olfactory receptor family 5 subfamily L 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016200185).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5L1	NM_001004738.2	c.175A>G	p.Met59Val	missense_variant	Exon 1 of 1	ENST00000625203.2	NP_001004738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5L1	ENST00000625203.2	c.175A>G	p.Met59Val	missense_variant	Exon 1 of 1	6	NM_001004738.2	ENSP00000485319.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151862 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000445 AC: 112 AN: 251444 Hom.: 2 AF XY: 0.000559 AC XY: 76 AN XY: 135896

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000185 AC: 271 AN: 1461792 Hom.: 3 Cov.: 33 AF XY: 0.000245 AC XY: 178 AN XY: 727208

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.0000459

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151980 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74284

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000279 Hom.: 0

ExAC AF: 0.000494 AC: 60

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175A>G (p.M59V) alteration is located in exon 1 (coding exon 1) of the OR5L1 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the methionine (M) at amino acid position 59 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	0.089
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.018
Eigen_PC	Benign	0.021
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Benign	0.22	T
Polyphen		0.0020	B
ClinPred		0.13	T
GERP RS		4.3
Varity_R		0.65
gMVP		0.15

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: rs377702509; hg19: chr11-55579117;