Genetic Variant RTP2:p.Thr64Ile (chr3-187698985-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004312.2(RTP2):c.191C>T(p.Thr64Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,592,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

RTP2
NM_001004312.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.178

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2943805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTP2	NM_001004312.2 link	c.191C>T	p.Thr64Ile	missense_variant	Exon 2 of 2	ENST00000358241.1	NP_001004312.2	Q5QGT7
RTP2	XM_017006301.2 link	c.191C>T	p.Thr64Ile	missense_variant	Exon 5 of 5		XP_016861790.1	Q5QGT7
RTP2	XM_017006302.2 link	c.191C>T	p.Thr64Ile	missense_variant	Exon 5 of 5		XP_016861791.1	Q5QGT7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTP2	ENST00000358241.1 link	c.191C>T	p.Thr64Ile	missense_variant	Exon 2 of 2	1	NM_001004312.2	ENSP00000350976.1		Q5QGT7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000246

AC:

AN:

244344

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

131818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000403

AC:

AN:

1440418

Hom.:

Cov.:

AF XY:

0.0000379

AC XY:

AN XY:

712012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000353

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000447

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000458

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.191C>T (p.T64I) alteration is located in exon 2 (coding exon 2) of the RTP2 gene. This alteration results from a C to T substitution at nucleotide position 191, causing the threonine (T) at amino acid position 64 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0058

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.11

Sift

Benign

0.046

Sift4G

Uncertain

0.020

Polyphen

0.97

Vest4

0.44

MutPred

0.51

Gain of MoRF binding (P = 0.0963);

MVP

0.26

MPC

0.19

ClinPred

0.82

GERP RS

4.3

Varity_R

0.33

gMVP

0.44

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