NM_206899.1:c.65C>T

Variant names:

• chr12-55636956-C-T
• NM_206899.1:c.65C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_206899.1(OR10P1):​c.65C>T​(p.Ala22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR10P1 NM_206899.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.884
• Publications: 0 publications found

Genes affected

OR10P1 (HGNC:15378): (olfactory receptor family 10 subfamily P member 1) 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]

ENSG00000258763 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048520833).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206899.1. 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
	OR10P1	NM_206899.1	MANE Select	c.65C>T	p.Ala22Val	missense	Exon 1 of 1	NP_996782.1	Q8NGE3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10P1	ENST00000309675.3	TSL:6 MANE Select	c.65C>T	p.Ala22Val	missense	Exon 1 of 1	ENSP00000308082.2	Q8NGE3
	ENSG00000258763	ENST00000715996.1		n.493+1958G>A		intron	N/A
	ENSG00000258763	ENST00000804081.1		n.231+438G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111804

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

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	0.083
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.057	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.88
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.032
Sift	Benign	0.060	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.26		Gain of ubiquitination at K21 (P = 0.1884)
MVP		0.13
MPC		0.091
ClinPred		0.061	T
GERP RS		1.3
PromoterAI		-0.026	Neutral
Varity_R		0.062
gMVP		0.34
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-56030740;