NM_001005522.2:c.430C>G

Variant names:

• chr1-247921447-C-G
• NM_001005522.2:c.430C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005522.2(OR2T8):​c.430C>G​(p.Leu144Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 3)
  • Exomes 𝑓: 0.0000040 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.12
• Publications: 0 publications found

Genes affected

OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040320992).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005522.2. 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
	OR2T8	NM_001005522.2	MANE Select	c.430C>G	p.Leu144Val	missense	Exon 2 of 2	NP_001005522.1	A6NH00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T8	ENST00000641945.2	MANE Select	c.430C>G	p.Leu144Val	missense	Exon 2 of 2	ENSP00000493286.1	A6NH00

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 14432 Hom.: 0 Cov.: 3

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000400 AC: 2 AN: 499634 Hom.: 1 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 259928

African (AFR) AF: 0.00 AC: 0 AN: 15450

American (AMR) AF: 0.00 AC: 0 AN: 18556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13658

East Asian (EAS) AF: 0.00 AC: 0 AN: 25012

South Asian (SAS) AF: 0.00 AC: 0 AN: 36412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1994

European-Non Finnish (NFE) AF: 0.00000606 AC: 2 AN: 329852

Other (OTH) AF: 0.00 AC: 0 AN: 27410

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 14432 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 6134

African (AFR) AF: 0.00 AC: 0 AN: 5124

American (AMR) AF: 0.00 AC: 0 AN: 1288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 334

East Asian (EAS) AF: 0.00 AC: 0 AN: 382

South Asian (SAS) AF: 0.00 AC: 0 AN: 358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 86

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6106

Other (OTH) AF: 0.00 AC: 0 AN: 206

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	Benign	0.071
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0040
DANN	Benign	0.24
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.00090	N
LIST_S2	Benign	0.020	T
M_CAP	Benign	0.00056	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.17	N
PhyloP100		-5.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.015
Sift	Benign	0.49	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.039
MutPred		0.38		Gain of methylation at R141 (P = 0.1359)
MVP		0.45
ClinPred		0.062	T
GERP RS		-7.1
Varity_R		0.032
gMVP		0.045
Mutation Taster		=100/0	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

hg19: chr1-248084749;