chr3-98354152-A-C

Variant names:

• chr3-98354152-A-C
• rs1707030147
• NM_001005517.1:c.299A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001005517.1(OR5K4):​c.299A>C​(p.Gln100Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q100K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR5K4 NM_001005517.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• Publications: 0 publications found

Genes affected

OR5K4 (HGNC:31291): (olfactory receptor family 5 subfamily K 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]

ENSG00000251088 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5K4	NM_001005517.1	c.299A>C	p.Gln100Pro	missense_variant	Exon 1 of 1	ENST00000354924.2	NP_001005517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5K4	ENST00000354924.2	c.299A>C	p.Gln100Pro	missense_variant	Exon 1 of 1	6	NM_001005517.1	ENSP00000347003.2
ENSG00000251088	ENST00000508616.1	n.188+11723A>C		intron_variant	Intron 3 of 3	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.299A>C (p.Q100P) alteration is located in exon 1 (coding exon 1) of the OR5K4 gene. This alteration results from a A to C substitution at nucleotide position 299, causing the glutamine (Q) at amino acid position 100 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	0.33
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0021	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	4.3	H
PhyloP100		5.6
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.69		Loss of catalytic residue at Q100 (P = 0.0222);
MVP		0.33
MPC		0.049
ClinPred		0.96	D
GERP RS		3.6
PromoterAI		0.024	Neutral
Varity_R		0.93
gMVP		0.60
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1707030147; hg19: chr3-98072996;