chr19-9126866-T-C

Position:

• chr19-9126866-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001958.1(OR7G3):​c.85A>G​(p.Met29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,612,858 control chromosomes in the GnomAD database, including 93,627 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (14321 hom., cov: 30)
  • Exomes 𝑓: 0.32 (79306 hom.)
• Consequence: OR7G3 NM_001001958.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

OR7G3 (HGNC:8467): (olfactory receptor family 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1384456E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7G3	NM_001001958.1	c.85A>G	p.Met29Val	missense_variant	1/1	ENST00000305444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7G3	ENST00000305444.2	c.85A>G	p.Met29Val	missense_variant	1/1		NM_001001958.1	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61216 AN: 151700 Hom.: 14297 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.347

GnomAD3 exomes AF: 0.324 AC: 81219 AN: 250856 Hom.: 14511 AF XY: 0.320 AC XY: 43415 AN XY: 135530

Gnomad AFR exome AF: 0.661

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.323

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.323 AC: 471274 AN: 1461040 Hom.: 79306 Cov.: 35 AF XY: 0.321 AC XY: 233556 AN XY: 726848

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.404 AC: 61279 AN: 151818 Hom.: 14321 Cov.: 30 AF XY: 0.399 AC XY: 29629 AN XY: 74192

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.345

Alfa AF: 0.321 Hom.: 20696

Bravo AF: 0.411

TwinsUK AF: 0.317 AC: 1176

ALSPAC AF: 0.320 AC: 1232

ESP6500AA AF: 0.653 AC: 2875

ESP6500EA AF: 0.311 AC: 2675

ExAC AF: 0.335 AC: 40613

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0060
DANN	Benign	0.40
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.025	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.5	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.021
Sift	Benign	0.045	D
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.011
MPC		0.085
ClinPred		0.0054	T
GERP RS		-8.0
Varity_R		0.077
gMVP		0.082

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

Publications

LitVar

Other links and lift over

dbSNP: rs10414255; hg19: chr19-9237542; COSMIC: COSV59640838; COSMIC: COSV59640838;