1-248488626-A-T

Variant names:

• chr1-248488626-A-T
• rs1770043
• NM_001004697.2:c.38A>T

Variant summary

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

The ENST00000641363.1(OR2T5):​c.38A>T​(p.Lys13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K13R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000019 (0 hom., cov: 7)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T5 ENST00000641363.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 15 publications found

Genes affected

OR2T5 (HGNC:15017): (olfactory receptor family 2 subfamily T member 5) 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]

ENSG00000229255 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.026132792).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641363.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T5	NM_001004697.2	MANE Select	c.38A>T	p.Lys13Met	missense	Exon 1 of 1	NP_001004697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T5	ENST00000641363.1	MANE Select	c.38A>T	p.Lys13Met	missense	Exon 1 of 1	ENSP00000493066.1
	ENSG00000229255	ENST00000450847.2	TSL:2	n.279-3142T>A		intron	N/A
	ENSG00000229255	ENST00000825060.1		n.326-3142T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000193 AC: 1 AN: 51792 Hom.: 0 Cov.: 7

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: 0.000221

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000240 AC: 27 AN: 112530 AF XY: 0.000337

Gnomad AFR exome AF: 0.000223

Gnomad AMR exome AF: 0.000258

Gnomad ASJ exome AF: 0.000212

Gnomad EAS exome AF: 0.000613

Gnomad FIN exome AF: 0.000242

Gnomad NFE exome AF: 0.000240

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000137 AC: 17 AN: 1242548 Hom.: 0 Cov.: 20 AF XY: 0.0000161 AC XY: 10 AN XY: 622768

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000104 AC: 2 AN: 19306

American (AMR) AF: 0.0000531 AC: 2 AN: 37636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22562

East Asian (EAS) AF: 0.0000853 AC: 3 AN: 35156

South Asian (SAS) AF: 0.0000802 AC: 6 AN: 74846

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5134

European-Non Finnish (NFE) AF: 0.00000316 AC: 3 AN: 948848

Other (OTH) AF: 0.00 AC: 0 AN: 50890

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000193 AC: 1 AN: 51816 Hom.: 0 Cov.: 7 AF XY: 0.0000398 AC XY: 1 AN XY: 25098

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3638

American (AMR) AF: 0.00 AC: 0 AN: 5592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1564

East Asian (EAS) AF: 0.00 AC: 0 AN: 1274

South Asian (SAS) AF: 0.00 AC: 0 AN: 792

European-Finnish (FIN) AF: 0.000221 AC: 1 AN: 4528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 33074

Other (OTH) AF: 0.00 AC: 0 AN: 740

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3329

ExAC AF: 0.000246 AC: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.1
DANN	Benign	0.80
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0033	N
M_CAP	Benign	0.00040	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-1.2
PrimateAI	Benign	0.18	T
Polyphen		0.040	B
MutPred		0.47		Loss of ubiquitination at K13 (P = 0.0244)
ClinPred		0.0081	T
GERP RS		-1.3
PromoterAI		0.011	Neutral
Varity_R		0.060
gMVP		0.14
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

dbSNP: rs1770043; hg19: chr1-248651927;