19-9251734-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001079935.2(OR7E24):c.691G>A(p.Gly231Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR7E24 NM_001079935.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.29

Genes affected

OR7E24 (HGNC:8396): (olfactory receptor family 7 subfamily E member 24) 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7E24	NM_001079935.2	c.691G>A	p.Gly231Arg	missense_variant	1/1	ENST00000456448.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7E24	ENST00000456448.3	c.691G>A	p.Gly231Arg	missense_variant	1/1		NM_001079935.2	P2
OR7E24	ENST00000641946.1	c.679G>A	p.Gly227Arg	missense_variant	2/2			A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460272 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726314

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

May 24, 2023

The c.691G>A (p.G231R) alteration is located in exon 1 (coding exon 1) of the OR7E24 gene. This alteration results from a G to A substitution at nucleotide position 691, causing the glycine (G) at amino acid position 231 to be replaced by an arginine (R). 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	0.30
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
Polyphen		1.0	.;D
Vest4		0.32
MutPred		0.82		.;Loss of glycosylation at S230 (P = 0.0427);
MVP		0.49
MPC		0.095
ClinPred		0.90	D
GERP RS		2.2
Varity_R		0.87

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: rs2066149322; hg19: chr19-9362410;