1-248273298-C-G

Position:

• chr1-248273298-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004695.2(OR2T33):​c.517G>C​(p.Asp173His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,458,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: OR2T33 NM_001004695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.22

Genes affected

OR2T33 (HGNC:31255): (olfactory receptor family 2 subfamily T member 33) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19276628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T33	NM_001004695.2	c.517G>C	p.Asp173His	missense_variant	2/2	ENST00000641220.1	NP_001004695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T33	ENST00000641220.1	c.517G>C	p.Asp173His	missense_variant	2/2		NM_001004695.2	ENSP00000493437.1
OR2T33	ENST00000318021.4	c.517G>C	p.Asp173His	missense_variant	1/1	6		ENSP00000324687.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1458928 Hom.: 0 Cov.: 51 AF XY: 0.00000689 AC XY: 5 AN XY: 725804

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: 0.00000900

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

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 04, 2024

The c.517G>C (p.D173H) alteration is located in exon 1 (coding exon 1) of the OR2T33 gene. This alteration results from a G to C substitution at nucleotide position 517, causing the aspartic acid (D) at amino acid position 173 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.0034	T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.96	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.063
Sift	Benign	0.38	.;T
Sift4G	Benign	0.51	.;T
Polyphen		1.0	D;D
Vest4		0.086
MutPred		0.49		Loss of stability (P = 0.0987);Loss of stability (P = 0.0987);
MVP		0.34
MPC		2.4
ClinPred		0.67	D
GERP RS		-3.5
Varity_R		0.099
gMVP		0.27

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: rs772644245; hg19: chr1-248436600;