Variant 12-123430542-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145058.3(RILPL2):c.457C>G(p.Leu153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000703 in 1,609,202 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 3 hom. )

Consequence

RILPL2
NM_145058.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

RILPL2 (HGNC:28787): (Rab interacting lysosomal protein like 2) This gene encodes a protein that contains a rab-interacting lysosomal protein-like domain. This protein may be involved in regulating lysosome morphology. This protein may also be a target for the Hepatitis C virus and assist in viral replication. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

RILPL2 links:

RILPL2 (HGNC:):

RILPL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.031508297).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RILPL2	NM_145058.3 linkuse as main transcript	c.457C>G	p.Leu153Val	missense_variant	2/4	ENST00000280571.10	NP_659495.1	Q969X0
RILPL2	XM_047428476.1 linkuse as main transcript	c.457C>G	p.Leu153Val	missense_variant	2/4		XP_047284432.1
RILPL2	XM_011538012.4 linkuse as main transcript	c.457C>G	p.Leu153Val	missense_variant	2/4		XP_011536314.1
RILPL2	NR_130703.2 linkuse as main transcript	n.603+5540C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RILPL2	ENST00000280571.10 linkuse as main transcript	c.457C>G	p.Leu153Val	missense_variant	2/4	1	NM_145058.3	ENSP00000280571.8		Q969X0

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000649

AC:

161

AN:

248044

Hom.:

AF XY:

0.000663

AC XY:

AN XY:

134308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000500

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000856

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000727

AC:

1059

AN:

1456926

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

522

AN XY:

724954

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000449

Gnomad4 ASJ exome

AF:

0.00204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000896

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000755

Gnomad4 OTH exome

AF:

0.000683

GnomAD4 genome

AF:

0.000473

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000781

Hom.:

Bravo

AF:

0.000635

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000626

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

Jul 12, 2023

The c.457C>G (p.L153V) alteration is located in exon 2 (coding exon 2) of the RILPL2 gene. This alteration results from a C to G substitution at nucleotide position 457, causing the leucine (L) at amino acid position 153 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Benign

0.13

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

M_CAP

Benign

0.019

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

REVEL

Benign

0.056

Sift

Benign

0.040

Sift4G

Benign

0.12

Polyphen

0.59

Vest4

0.42

MVP

0.51

MPC

1.1

ClinPred

0.051

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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