11-6002694-C-A

Variant summary

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

The NM_001005179.4(OR56A4):c.299G>T(p.Cys100Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,890 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: 0.000013 (0 hom.)
• Consequence: OR56A4 NM_001005179.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

Genes affected

OR56A4 (HGNC:14791): (olfactory receptor family 56 subfamily A member 4) 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]

OR56A3 (HGNC:):

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, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR56A4	NM_001005179.4	c.299G>T	p.Cys100Phe	missense_variant	3/3	ENST00000641156.1
OR56A3	XM_047426926.1	c.*469-1026C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR56A4	ENST00000641156.1	c.299G>T	p.Cys100Phe	missense_variant	3/3		NM_001005179.4	P1
OR56A4	ENST00000330728.4	c.455G>T	p.Cys152Phe	missense_variant	1/1
OR56A4	ENST00000641279.1	c.299G>T	p.Cys100Phe	missense_variant	1/1			P1
OR56A4	ENST00000641835.1	c.299G>T	p.Cys100Phe	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727246

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: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 01, 2022

The c.455G>T (p.C152F) alteration is located in exon 1 (coding exon 1) of the OR56A4 gene. This alteration results from a G to T substitution at nucleotide position 455, causing the cysteine (C) at amino acid position 152 to be replaced by a phenylalanine (F). 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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0047	T
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	H;H;H;.
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.28	T
Polyphen		0.99	D;D;D;.
Vest4		0.82
MutPred		0.58		Loss of catalytic residue at C100 (P = 0.031);Loss of catalytic residue at C100 (P = 0.031);Loss of catalytic residue at C100 (P = 0.031);.;
MVP		0.64
MPC		0.50
ClinPred		1.0	D
GERP RS		2.4
Varity_R		0.90
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-6023924;