Variant 11-56613052-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004740.2(OR5M1):c.451T>C(p.Tyr151His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,611,482 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 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 3 hom. )

Consequence

OR5M1
NM_001004740.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0240

Variant links:

Genes affected

OR5M1 (HGNC:8352): (olfactory receptor family 5 subfamily M 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]

OR5M1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061325043).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M1	NM_001004740.2 linkuse as main transcript	c.451T>C	p.Tyr151His	missense_variant	2/2	ENST00000641076.1	NP_001004740.1	Q8NGP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5M1	ENST00000641076.1 linkuse as main transcript	c.451T>C	p.Tyr151His	missense_variant	2/2		NM_001004740.2	ENSP00000493124.1		Q8NGP8

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149892

Hom.:

Cov.:

show subpopulations

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:

0.000853

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000926

AC:

AN:

248292

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134634

show subpopulations

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:

0.000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727072

show subpopulations

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:

0.000707

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149892

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73238

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000853

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.451T>C (p.Y151H) alteration is located in exon 1 (coding exon 1) of the OR5M1 gene. This alteration results from a T to C substitution at nucleotide position 451, causing the tyrosine (Y) at amino acid position 151 to be replaced by a histidine (H). 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

0.27

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.064

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-4.3

.;D

REVEL

Benign

0.10

Sift

Uncertain

0.017

.;D

Sift4G

Benign

0.26

.;T

Polyphen

0.026

B;B

Vest4

0.10

MutPred

0.33

Gain of glycosylation at S155 (P = 0.124);Gain of glycosylation at S155 (P = 0.124);

MVP

0.49

MPC

0.43

ClinPred

0.078

GERP RS

3.7

Varity_R

0.19

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over