1-247921315-T-A

Variant names:

• chr1-247921315-T-A
• rs1412363328
• NM_001005522.2:c.298T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005522.2(OR2T8):​c.298T>A​(p.Phe100Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000012 (0 hom., cov: 10)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T8 NM_001005522.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17656204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2	c.298T>A	p.Phe100Ile	missense_variant	Exon 2 of 2	ENST00000641945.2	NP_001005522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T8	ENST00000641945.2	c.298T>A	p.Phe100Ile	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1

Frequencies

GnomAD3 genomes AF: 0.0000121 AC: 1 AN: 82564 Hom.: 0 Cov.: 10

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: 0.0000241

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 744940 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 382374

African (AFR) AF: 0.00 AC: 0 AN: 20744

American (AMR) AF: 0.00 AC: 0 AN: 29954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18052

East Asian (EAS) AF: 0.00 AC: 0 AN: 32996

South Asian (SAS) AF: 0.00 AC: 0 AN: 55356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 503404

Other (OTH) AF: 0.00 AC: 0 AN: 36228

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000121 AC: 1 AN: 82564 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 37088

African (AFR) AF: 0.00 AC: 0 AN: 20628

American (AMR) AF: 0.00 AC: 0 AN: 6710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2272

East Asian (EAS) AF: 0.00 AC: 0 AN: 3048

South Asian (SAS) AF: 0.00 AC: 0 AN: 1910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.0000241 AC: 1 AN: 41550

Other (OTH) AF: 0.00 AC: 0 AN: 1022

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298T>A (p.F100I) alteration is located in exon 1 (coding exon 1) of the OR2T8 gene. This alteration results from a T to A substitution at nucleotide position 298, causing the phenylalanine (F) at amino acid position 100 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M;M
PhyloP100		2.5
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.7	.;D
REVEL	Benign	0.092
Sift	Uncertain	0.012	.;D
Sift4G	Uncertain	0.017	.;D
Polyphen		0.076	B;B
Vest4		0.42
MutPred		0.42		Gain of catalytic residue at L105 (P = 0.1251);Gain of catalytic residue at L105 (P = 0.1251);
MVP		0.72
ClinPred		0.79	D
GERP RS		1.3
Varity_R		0.57
gMVP		0.22
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1412363328; hg19: chr1-248084617;