NM_001005173.3:c.911C>T

Variant names:

• chr11-5986020-G-A
• rs201296821
• NM_001005173.3:c.911C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005173.3(OR52L1):​c.911C>T​(p.Ala304Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: OR52L1 NM_001005173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.928
• Publications: 3 publications found

Genes affected

OR52L1 (HGNC:14785): (olfactory receptor family 52 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. [provided by RefSeq, Jul 2008]

OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.085879356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005173.3. 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
	OR52L1	NM_001005173.3	MANE Select	c.911C>T	p.Ala304Val	missense	Exon 1 of 1	NP_001005173.3	Q8NGH7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52L1	ENST00000332249.4	TSL:6 MANE Select	c.911C>T	p.Ala304Val	missense	Exon 1 of 1	ENSP00000330338.4	Q8NGH7

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000137 AC: 34 AN: 247608 AF XY: 0.000156

Gnomad AFR exome AF: 0.000197

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000174 AC: 254 AN: 1460880 Hom.: 1 Cov.: 31 AF XY: 0.000193 AC XY: 140 AN XY: 726674

African (AFR) AF: 0.000179 AC: 6 AN: 33470

American (AMR) AF: 0.0000673 AC: 3 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000189 AC: 210 AN: 1111454

Other (OTH) AF: 0.000133 AC: 8 AN: 60354

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74448

African (AFR) AF: 0.000289 AC: 12 AN: 41548

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000195 Hom.: 0

Bravo AF: 0.000159

ESP6500AA AF: 0.000241 AC: 1

ESP6500EA AF: 0.000355 AC: 3

ExAC AF: 0.000165 AC: 20

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	0.097
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.017	N
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.93
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.15
Sift	Benign	0.37	T
Sift4G	Benign	0.41	T
Vest4		0.047
MVP		0.41
MPC		0.14
ClinPred		0.048	T
GERP RS		2.7
gMVP		0.11
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs201296821; hg19: chr11-6007250; COSMIC: COSV100176303;