Variant 3-187698925-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004312.2(RTP2):c.251C>A(p.Ala84Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,609,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

RTP2
NM_001004312.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07

Variant links:

Genes affected

RTP2 (HGNC:32486): (receptor transporter protein 2) Enables olfactory receptor binding activity. Involved in protein insertion into membrane. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

RTP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012237281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTP2	NM_001004312.2 linkuse as main transcript	c.251C>A	p.Ala84Glu	missense_variant	2/2	ENST00000358241.1	NP_001004312.2	Q5QGT7
RTP2	XM_017006301.2 linkuse as main transcript	c.251C>A	p.Ala84Glu	missense_variant	5/5		XP_016861790.1	Q5QGT7
RTP2	XM_017006302.2 linkuse as main transcript	c.251C>A	p.Ala84Glu	missense_variant	5/5		XP_016861791.1	Q5QGT7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTP2	ENST00000358241.1 linkuse as main transcript	c.251C>A	p.Ala84Glu	missense_variant	2/2	1	NM_001004312.2	ENSP00000350976.1		Q5QGT7

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000347

AC:

AN:

248186

Hom.:

AF XY:

0.000409

AC XY:

AN XY:

134614

show subpopulations

Gnomad AFR exome

AF:

0.0000637

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000627

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000438

AC:

638

AN:

1457668

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

313

AN XY:

724194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000557

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000516

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000565

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000244

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000330

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.00136

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.251C>A (p.A84E) alteration is located in exon 2 (coding exon 2) of the RTP2 gene. This alteration results from a C to A substitution at nucleotide position 251, causing the alanine (A) at amino acid position 84 to be replaced by a glutamic acid (E). 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

0.19

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.018

DANN

Benign

0.74

DEOGEN2

Benign

0.012

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.52

M_CAP

Benign

0.0046

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PrimateAI

Benign

0.42

PROVEAN

Benign

0.48

REVEL

Benign

0.026

Sift

Benign

1.0

Sift4G

Benign

0.064

Polyphen

0.41

Vest4

0.069

MVP

0.014

MPC

0.067

ClinPred

0.040

GERP RS

-7.3

Varity_R

0.055

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over