rs143884236

Variant names:

• chr14-21570041-C-T
• rs143884236
• NM_001005465.2:c.704G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-21570041-C-T
• chr14-21570041-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001005465.2(OR10G3):​c.704G>A​(p.Arg235Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 1,614,224 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R235W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0057 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (65 hom.)
• Consequence: OR10G3 NM_001005465.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15
• Publications: 9 publications found

Genes affected

OR10G3 (HGNC:8171): (olfactory receptor family 10 subfamily G member 3) 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004649371).
• BP6: Variant 14-21570041-C-T is Benign according to our data. Variant chr14-21570041-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005465.2. 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
	OR10G3	NM_001005465.2	MANE Select	c.704G>A	p.Arg235Gln	missense	Exon 2 of 2	NP_001005465.1	Q8NGC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10G3	ENST00000641040.1	MANE Select	c.704G>A	p.Arg235Gln	missense	Exon 2 of 2	ENSP00000493245.1	Q8NGC4
	OR10G3	ENST00000641185.1		c.704G>A	p.Arg235Gln	missense	Exon 3 of 3	ENSP00000492973.1	Q8NGC4
	OR10G3	ENST00000641655.1		n.332G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 861 AN: 152224 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00780

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.00642 AC: 1614 AN: 251314 AF XY: 0.00635

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.0253

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00619

Gnomad NFE exome AF: 0.00876

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00736 AC: 10759 AN: 1461882 Hom.: 65 Cov.: 49 AF XY: 0.00735 AC XY: 5348 AN XY: 727244

African (AFR) AF: 0.00203 AC: 68 AN: 33480

American (AMR) AF: 0.00510 AC: 228 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 592 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86254

European-Finnish (FIN) AF: 0.00723 AC: 386 AN: 53420

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.00810 AC: 9010 AN: 1112010

Other (OTH) AF: 0.00724 AC: 437 AN: 60392

GnomAD4 genome AF: 0.00565 AC: 861 AN: 152342 Hom.: 7 Cov.: 32 AF XY: 0.00548 AC XY: 408 AN XY: 74498

African (AFR) AF: 0.00159 AC: 66 AN: 41576

American (AMR) AF: 0.00575 AC: 88 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00574 AC: 61 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00780 AC: 531 AN: 68038

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.00803 Hom.: 29

Bravo AF: 0.00581

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00884 AC: 76

ExAC AF: 0.00612 AC: 743

EpiCase AF: 0.00981

EpiControl AF: 0.0101

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.084
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.055	T
Polyphen		0.28	B
Vest4		0.17
MVP		0.38
MPC		0.054
ClinPred		0.028	T
GERP RS		4.2
Varity_R		0.33
gMVP		0.22
Mutation Taster		=99/1	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: rs143884236; hg19: chr14-22038172; COSMIC: COSV99063751; COSMIC: COSV99063751;