1-248559302-A-C

Variant names:

• chr1-248559302-A-C
• rs2103074728
• NM_001004694.3:c.190T>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004694.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T29	NM_001004694.3	MANE Select	c.190T>G	p.Tyr64Asp	missense	Exon 2 of 2	NP_001004694.2	Q8NH02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T29	ENST00000641069.1	MANE Select	c.190T>G	p.Tyr64Asp	missense	Exon 2 of 2	ENSP00000492895.1	Q8NH02
	OR2T29	ENST00000328570.6	TSL:6	c.190T>G	p.Tyr64Asp	missense	Exon 1 of 1	ENSP00000331774.3	Q8NH02
	ENSG00000224521	ENST00000436515.2	TSL:2	n.147-3298A>C		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 28650

American (AMR) AF: 0.00 AC: 0 AN: 42542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23038

East Asian (EAS) AF: 0.00 AC: 0 AN: 36876

South Asian (SAS) AF: 0.00 AC: 0 AN: 79728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4502

European-Non Finnish (NFE) AF: 0.00000383 AC: 3 AN: 783174

Other (OTH) AF: 0.00 AC: 0 AN: 48380

GnomAD4 genome Cov.: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	4.5	H
PhyloP100		4.7
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
Vest4		0.71
MutPred		0.67		Loss of catalytic residue at S68 (P = 0.1192)
MVP		0.70
MPC		5.0
ClinPred		1.0	D
GERP RS		2.7
PromoterAI		-0.0092	Neutral
Varity_R		0.98
gMVP		0.37
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs2103074728; hg19: chr1-248722603;