chr11-56577108-A-G

Variant names:

• chr11-56577108-A-G
• rs754657986
• NM_001004741.1:c.614T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004741.1(OR5M10):​c.614T>C​(p.Phe205Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: OR5M10 NM_001004741.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03752339).

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.614T>C	p.Phe205Ser	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.614T>C	p.Phe205Ser	missense	Exon 1 of 1	ENSP00000435416.2	Q6IEU7

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152118 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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: 0.0000201 AC: 5 AN: 249196 AF XY: 0.00000740

Gnomad AFR exome AF: 0.000323

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461622 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 727098

African (AFR) AF: 0.000299 AC: 10 AN: 33458

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111828

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152118 Hom.: 1 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74320

African (AFR) AF: 0.000459 AC: 19 AN: 41362

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

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

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000159

ExAC AF: 0.0000248 AC: 3

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	0.20
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.25	N
PhyloP100		0.33
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.028
Sift	Benign	0.12	T
Sift4G	Benign	0.22	T
Polyphen		0.025	B
Vest4		0.094
MVP		0.25
MPC		0.56
ClinPred		0.049	T
GERP RS		1.8
Varity_R		0.17
gMVP		0.24
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754657986; hg19: chr11-56344584;