chr19-9126575-T-C

Position:

• chr19-9126575-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001958.1(OR7G3):​c.376A>G​(p.Ile126Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR7G3 NM_001001958.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29954207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7G3	NM_001001958.1	c.376A>G	p.Ile126Val	missense_variant	1/1	ENST00000305444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7G3	ENST00000305444.2	c.376A>G	p.Ile126Val	missense_variant	1/1		NM_001001958.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251446 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.376A>G (p.I126V) alteration is located in exon 1 (coding exon 1) of the OR7G3 gene. This alteration results from a A to G substitution at nucleotide position 376, causing the isoleucine (I) at amino acid position 126 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0062	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	0.89	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.18
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.39		Gain of methylation at R122 (P = 0.2395);
MVP		0.59
MPC		0.39
ClinPred		0.82	D
GERP RS		4.0
Varity_R		0.26
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs748706910; hg19: chr19-9237251;