19-9251264-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001079935.2(OR7E24):c.221A>C(p.His74Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR7E24 NM_001079935.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

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 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7E24	NM_001079935.2	c.221A>C	p.His74Pro	missense_variant	1/1	ENST00000456448.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7E24	ENST00000456448.3	c.221A>C	p.His74Pro	missense_variant	1/1		NM_001079935.2	P2
OR7E24	ENST00000641946.1	c.209A>C	p.His70Pro	missense_variant	2/2			A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 21 AN: 151734 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000969

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00319 AC: 4633 AN: 1450218 Hom.: 0 Cov.: 34 AF XY: 0.00306 AC XY: 2209 AN XY: 721898

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00146

Gnomad4 EAS exome AF: 0.000961

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000319

Gnomad4 NFE exome AF: 0.00380

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000138 AC: 21 AN: 151856 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74204

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000971

Gnomad4 SAS AF: 0.000627

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

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

Mar 16, 2022

The c.221A>C (p.H74P) alteration is located in exon 1 (coding exon 1) of the OR7E24 gene. This alteration results from a A to C substitution at nucleotide position 221, causing the histidine (H) at amino acid position 74 to be replaced by a proline (P). 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	0.25
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	22
Dann	Benign	0.97
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	0.74	D
PrimateAI	Benign	0.22	T
Polyphen		0.16	.;B
Vest4		0.51
MutPred		0.74		.;Gain of glycosylation at T75 (P = 0.068);
MVP		0.33
MPC		0.021
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.93

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: rs2066145753; hg19: chr19-9361940;