Variant 11-56576901-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004741.1(OR5M10):c.821T>C(p.Ile274Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00092 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

OR5M10
NM_001004741.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.374

Variant links:

Genes affected

OR5M10 (HGNC:15290): (olfactory receptor family 5 subfamily M member 10) 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]

OR5M10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018944442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5M10	NM_001004741.1 linkuse as main transcript	c.821T>C	p.Ile274Thr	missense_variant	1/1	ENST00000526538.2	NP_001004741.1	Q6IEU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5M10	ENST00000526538.2 linkuse as main transcript	c.821T>C	p.Ile274Thr	missense_variant	1/1	6	NM_001004741.1	ENSP00000435416.2		Q6IEU7

Frequencies

GnomAD3 genomes

AF:

0.000921

AC:

140

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000774

AC:

193

AN:

249212

Hom.:

AF XY:

0.000851

AC XY:

115

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.000696

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00114

AC:

1670

AN:

1461322

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

833

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000557

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152208

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.000888

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000960

AC:

116

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

Aug 17, 2021

The c.821T>C (p.I274T) alteration is located in exon 1 (coding exon 1) of the OR5M10 gene. This alteration results from a T to C substitution at nucleotide position 821, causing the isoleucine (I) at amino acid position 274 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.1

DANN

Benign

0.71

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.43

M_CAP

Benign

0.0070

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.043

Sift

Benign

0.10

Sift4G

Benign

0.15

Polyphen

0.025

Vest4

0.064

MVP

0.20

MPC

0.13

ClinPred

0.0028

GERP RS

3.1

Varity_R

0.069

gMVP

0.066

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

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