NM_001004741.1:c.932G>A

Variant names:

• chr11-56576790-C-T
• rs754935666
• NM_001004741.1:c.932G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004741.1(OR5M10):​c.932G>A​(p.Cys311Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000808 in 1,608,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C311R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: OR5M10 NM_001004741.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0900
• Publications: 2 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042475045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004741.1. 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
	OR5M10	NM_001004741.1	MANE Select	c.932G>A	p.Cys311Tyr	missense	Exon 1 of 1	NP_001004741.1	Q6IEU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5M10	ENST00000526538.2	TSL:6 MANE Select	c.932G>A	p.Cys311Tyr	missense	Exon 1 of 1	ENSP00000435416.2	Q6IEU7

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000818 AC: 2 AN: 244432 AF XY: 0.0000151

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1456776 Hom.: 0 Cov.: 32 AF XY: 0.00000828 AC XY: 6 AN XY: 724504

African (AFR) AF: 0.00 AC: 0 AN: 33118

American (AMR) AF: 0.00 AC: 0 AN: 43726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000352 AC: 3 AN: 85312

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1110064

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151990 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74242

African (AFR) AF: 0.0000484 AC: 2 AN: 41318

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

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	0.074
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.4
DANN	Benign	0.18
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.99	L
PhyloP100		-0.090
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.073
Sift	Benign	1.0	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.077
MVP		0.040
MPC		0.16
ClinPred		0.037	T
GERP RS		-7.9
Varity_R		0.037
gMVP		0.075
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs754935666; hg19: chr11-56344266; COSMIC: COSV73242238;