NM_001004462.2:c.65A>G

Variant names:

• chr11-124015639-A-G
• rs771911510
• NM_001004462.2:c.65A>G

Variant summary

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

The NM_001004462.2(OR10G4):​c.65A>G​(p.Asp22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,604,818 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: OR10G4 NM_001004462.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 1 publications found

Genes affected

OR10G4 (HGNC:14809): (olfactory receptor family 10 subfamily G member 4) 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=0.05711502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004462.2. 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
	OR10G4	NM_001004462.2	MANE Select	c.65A>G	p.Asp22Gly	missense	Exon 2 of 2	NP_001004462.1	A0A126GWS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10G4	ENST00000641722.1	MANE Select	c.65A>G	p.Asp22Gly	missense	Exon 2 of 2	ENSP00000493036.1	Q8NGN3
	OR10G4	ENST00000641521.1		c.65A>G	p.Asp22Gly	missense	Exon 3 of 3	ENSP00000493354.1	Q8NGN3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152012 Hom.: 0 Cov.: 30

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: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000246 AC: 6 AN: 243904 AF XY: 0.0000303

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000332

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1452806 Hom.: 0 Cov.: 62 AF XY: 0.00000554 AC XY: 4 AN XY: 722198

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 42480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25644

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39646

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107498

Other (OTH) AF: 0.00 AC: 0 AN: 60064

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152012 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74228

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.85	N
PhyloP100		2.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.077
Sift	Benign	0.17	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.12
MutPred		0.59		Gain of helix (P = 0.0854)
MVP		0.30
MPC		0.63
ClinPred		0.045	T
GERP RS		2.4
Varity_R		0.11
gMVP		0.53
Mutation Taster		=96/4	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: rs771911510; hg19: chr11-123886346;