3-98470315-T-C

Position:

• chr3-98470315-T-C

Variant summary

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

The NM_001004736.4(OR5K1):​c.739T>C​(p.Ser247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR5K1 NM_001004736.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.735

Genes affected

OR5K1 (HGNC:8349): (olfactory receptor family 5 subfamily K member 1) 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=0.3944743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5K1	NM_001004736.4	c.739T>C	p.Ser247Pro	missense_variant	2/2	ENST00000642057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5K1	ENST00000642057.1	c.739T>C	p.Ser247Pro	missense_variant	2/2		NM_001004736.4	P1
OR5K1	ENST00000332650.5	c.739T>C	p.Ser247Pro	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461160 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000227

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.739T>C (p.S247P) alteration is located in exon 1 (coding exon 1) of the OR5K1 gene. This alteration results from a T to C substitution at nucleotide position 739, causing the serine (S) at amino acid position 247 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0095	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.57	.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Benign	0.12
Sift	Uncertain	0.0070	.;D
Sift4G	Uncertain	0.018	.;D
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.69		Loss of catalytic residue at S247 (P = 0.0676);Loss of catalytic residue at S247 (P = 0.0676);
MVP		0.71
MPC		0.13
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.98
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1705431541; hg19: chr3-98189159;