1-248638804-C-A

Position:

• chr1-248638804-C-A

Variant summary

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

The NM_001001827.2(OR2T35):​c.455G>T​(p.Gly152Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000090 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T35 NM_001001827.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0720

Genes affected

OR2T35 (HGNC:31257): (olfactory receptor family 2 subfamily T member 35) 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T35	NM_001001827.2	c.455G>T	p.Gly152Val	missense_variant	2/2	ENST00000641268.1	NP_001001827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T35	ENST00000641268.1	c.455G>T	p.Gly152Val	missense_variant	2/2		NM_001001827.2	ENSP00000492995.1

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000902 AC: 9 AN: 997640 Hom.: 0 Cov.: 14 AF XY: 0.00000977 AC XY: 5 AN XY: 511810

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: 0.0000115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 8

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

Nov 03, 2023

The c.455G>T (p.G152V) alteration is located in exon 1 (coding exon 1) of the OR2T35 gene. This alteration results from a G to T substitution at nucleotide position 455, causing the glycine (G) at amino acid position 152 to be replaced by a valine (V). 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	0.44
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.0077	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-8.8	.;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		1.0	D;D
Vest4		0.56
MutPred		0.71		Gain of MoRF binding (P = 0.3928);Gain of MoRF binding (P = 0.3928);
MVP		0.73
MPC		3.3
ClinPred		0.92	D
GERP RS		2.9
Varity_R		0.90
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs1331906276; hg19: chr1-248802105;