1-248559302-A-C

Position:

• chr1-248559302-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001004694.3(OR2T29):​c.190T>G​(p.Tyr64Asp) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T29 NM_001004694.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

Genes affected

OR2T29 (HGNC:31253): (olfactory receptor family 2 subfamily T member 29) 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]

ENSG00000224521 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T29	NM_001004694.3	c.190T>G	p.Tyr64Asp	missense_variant	2/2	ENST00000641069.1	NP_001004694.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T29	ENST00000641069.1	c.190T>G	p.Tyr64Asp	missense_variant	2/2		NM_001004694.3	ENSP00000492895.1
OR2T29	ENST00000328570.6	c.190T>G	p.Tyr64Asp	missense_variant	1/1	6		ENSP00000331774.3
ENSG00000224521	ENST00000438623.1	n.92-3298A>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000273 AC: 3 AN: 1097598 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 559264

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: 0.00000383

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

Jun 16, 2023

The c.190T>G (p.Y64D) alteration is located in exon 1 (coding exon 1) of the OR2T29 gene. This alteration results from a T to G substitution at nucleotide position 190, causing the tyrosine (Y) at amino acid position 64 to be replaced by an aspartic acid (D). 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	0.43
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.0033	T
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	4.5	H;H
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-9.1	.;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	D;D
Vest4		0.71
MutPred		0.67		Loss of catalytic residue at S68 (P = 0.1192);Loss of catalytic residue at S68 (P = 0.1192);
MVP		0.70
MPC		5.0
ClinPred		1.0	D
GERP RS		2.7
Varity_R		0.98
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-248722603;