chr14-21570041-C-T

Position:

• chr14-21570041-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/21 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

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

Verdict is Benign. Variant got -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 id is 2644070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10G3	NM_001005465.2	c.704G>A	p.Arg235Gln	missense_variant	2/2	ENST00000641040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10G3	ENST00000641040.1	c.704G>A	p.Arg235Gln	missense_variant	2/2		NM_001005465.2	P1
OR10G3	ENST00000641185.1	c.704G>A	p.Arg235Gln	missense_variant	3/3			P1
OR10G3	ENST00000641655.1	n.332G>A		non_coding_transcript_exon_variant	2/2

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

GnomAD3 exomes AF: 0.00642 AC: 1614 AN: 251314 Hom.: 14 AF XY: 0.00635 AC XY: 863 AN XY: 135816

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 SAS exome AF: 0.0000653

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

Gnomad4 AFR exome AF: 0.00203

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00723

Gnomad4 NFE exome AF: 0.00810

Gnomad4 OTH exome AF: 0.00724

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

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.00780

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00843 Hom.: 24

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

OR10G3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

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;T;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;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.57	D
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;B;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

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

Other links and lift over

dbSNP: rs143884236; hg19: chr14-22038172; COSMIC: COSV99063751; COSMIC: COSV99063751;