Variant chr3-187199711-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000312295.5(RTP1):c.433A>C(p.Met145Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,270 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M145T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

RTP1
ENST00000312295.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

RTP1 (HGNC:28580): (receptor transporter protein 1) Enables olfactory receptor binding activity. Involved in protein insertion into membrane. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

RTP1 links:

ENSG00000198491 (HGNC:):

ENSG00000198491 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21296161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTP1	NM_153708.3 linkuse as main transcript	c.433A>C	p.Met145Leu	missense_variant	2/2	ENST00000312295.5	NP_714919.2	P59025
LOC101929106	NR_110052.1 linkuse as main transcript	n.1074T>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTP1	ENST00000312295.5 linkuse as main transcript	c.433A>C	p.Met145Leu	missense_variant	2/2	1	NM_153708.3	ENSP00000311712.4		P59025
ENSG00000198491	ENST00000356133.3 linkuse as main transcript	n.1074T>G		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250076

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461076

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

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 18, 2021

The c.433A>C (p.M145L) alteration is located in exon 2 (coding exon 2) of the RTP1 gene. This alteration results from a A to C substitution at nucleotide position 433, causing the methionine (M) at amino acid position 145 to be replaced by a leucine (L). 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

0.36

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

M_CAP

Benign

0.0054

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.40

REVEL

Benign

0.13

Sift

Benign

0.13

Sift4G

Benign

0.13

Polyphen

0.92

Vest4

0.36

MutPred

0.43

Loss of helix (P = 0.079);

MVP

0.36

MPC

0.69

ClinPred

0.48

GERP RS

5.7

Varity_R

0.35

gMVP

0.45

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