Variant 2-241869829-G-A 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_173821.3(RTP5):c.73G>A(p.Val25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,575,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

RTP5
NM_173821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

RTP5 (HGNC:26585): (receptor transporter protein 5 (putative)) Predicted to enable olfactory receptor binding activity. Predicted to be involved in detection of chemical stimulus involved in sensory perception of bitter taste; protein insertion into membrane; and protein targeting to membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RTP5 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=0.03914717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTP5	NM_173821.3 linkuse as main transcript	c.73G>A	p.Val25Ile	missense_variant	1/2	ENST00000343216.3	NP_776182.2	Q14D33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTP5	ENST00000343216.3 linkuse as main transcript	c.73G>A	p.Val25Ile	missense_variant	1/2	1	NM_173821.3	ENSP00000345374.3		Q14D33
RTP5	ENST00000419912.1 linkuse as main transcript	n.73G>A		non_coding_transcript_exon_variant	1/3	5		ENSP00000397191.1		F8WB75

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

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:

0.0000631

AC:

AN:

190230

Hom.:

AF XY:

0.0000484

AC XY:

AN XY:

103406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000445

Gnomad SAS exome

AF:

0.0000801

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000238

Gnomad OTH exome

AF:

0.000206

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1422968

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

704972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

Gnomad4 AMR exome

AF:

0.0000253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000161

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000192

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000280

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000584

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 06, 2023

The c.73G>A (p.V25I) alteration is located in exon 1 (coding exon 1) of the RTP5 gene. This alteration results from a G to A substitution at nucleotide position 73, causing the valine (V) at amino acid position 25 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

Benign

0.096

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.88

DANN

Benign

0.80

DEOGEN2

Benign

0.0076

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.41

M_CAP

Benign

0.0021

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.53

REVEL

Benign

0.0070

Sift

Benign

0.44

Sift4G

Benign

0.51

Polyphen

0.011

Vest4

0.15

MutPred

0.25

Loss of ubiquitination at K21 (P = 0.1139);

MVP

0.030

MPC

0.14

ClinPred

0.0072

GERP RS

-2.4

Varity_R

0.022

gMVP

0.14

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