1-248593570-A-G

Position:

• chr1-248593570-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001004693.2(OR2T10):​c.199T>C​(p.Ser67Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,426,100 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000035 (2 hom.)
• Consequence: OR2T10 NM_001004693.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.241

Genes affected

OR2T10 (HGNC:19573): (olfactory receptor family 2 subfamily T member 10) 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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33207017).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T10	NM_001004693.2	c.199T>C	p.Ser67Pro	missense_variant	2/2	ENST00000642090.1	NP_001004693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T10	ENST00000642090.1	c.199T>C	p.Ser67Pro	missense_variant	2/2		NM_001004693.2	ENSP00000493236	P1
OR2T10	ENST00000330500.4	c.199T>C	p.Ser67Pro	missense_variant	1/1			ENSP00000329210	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000351 AC: 5 AN: 1426100 Hom.: 2 Cov.: 31 AF XY: 0.00000282 AC XY: 2 AN XY: 710028

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: 0.0000237

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000276

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

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

Jan 17, 2023

The c.199T>C (p.S67P) alteration is located in exon 1 (coding exon 1) of the OR2T10 gene. This alteration results from a T to C substitution at nucleotide position 199, causing the serine (S) at amino acid position 67 to be replaced by a proline (P). 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	0.49
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	0.060
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.4	.;D
REVEL	Benign	0.044
Sift	Uncertain	0.0010	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		1.0	D;D
Vest4		0.29
MutPred		0.60		Loss of stability (P = 0.111);Loss of stability (P = 0.111);
MVP		0.36
MPC		0.41
ClinPred		0.99	D
GERP RS		0.99
Varity_R		0.94
gMVP		0.70

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

LitVar

Other links and lift over

dbSNP: rs1660047373; hg19: chr1-248756871;