chr1-248488776-T-C

Position:

• chr1-248488776-T-C

Variant summary

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

The NM_001004697.2(OR2T5):​c.188T>C​(p.Met63Thr) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T5 NM_001004697.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86

Genes affected

OR2T5 (HGNC:15017): (olfactory receptor family 2 subfamily T member 5) 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]

LOC105373277 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T5	NM_001004697.2	c.188T>C	p.Met63Thr	missense_variant	1/1	ENST00000641363.1
LOC105373277	XR_002958498.2	n.188-3292A>G		intron_variant, non_coding_transcript_variant
LOC105373277	XR_001738575.2	n.144-3292A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T5	ENST00000641363.1	c.188T>C	p.Met63Thr	missense_variant	1/1		NM_001004697.2	P1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.65e-7 AC: 1 AN: 1307512 Hom.: 0 Cov.: 23 AF XY: 0.00000152 AC XY: 1 AN XY: 658052

Gnomad4 AFR exome AF: 0.0000418

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 14

Bravo AF: 0.00000378

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

Jan 18, 2023

The c.188T>C (p.M63T) alteration is located in exon 1 (coding exon 1) of the OR2T5 gene. This alteration results from a T to C substitution at nucleotide position 188, causing the methionine (M) at amino acid position 63 to be replaced by a threonine (T). 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	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.000070
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0012	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.33	T
Polyphen		0.26	B
MutPred		0.68		Gain of glycosylation at M63 (P = 0.0739);
ClinPred		0.97	D
GERP RS		2.6
Varity_R		0.78
gMVP		0.16

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: rs1663878759; hg19: chr1-248652077;