Variant 12-123430634-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145058.3(RILPL2):c.365T>C(p.Val122Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,602,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

RILPL2
NM_145058.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RILPL2	NM_145058.3 linkuse as main transcript	c.365T>C	p.Val122Ala	missense_variant	2/4	ENST00000280571.10	NP_659495.1	Q969X0
RILPL2	XM_047428476.1 linkuse as main transcript	c.365T>C	p.Val122Ala	missense_variant	2/4		XP_047284432.1
RILPL2	XM_011538012.4 linkuse as main transcript	c.365T>C	p.Val122Ala	missense_variant	2/4		XP_011536314.1
RILPL2	NR_130703.2 linkuse as main transcript	n.603+5448T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RILPL2	ENST00000280571.10 linkuse as main transcript	c.365T>C	p.Val122Ala	missense_variant	2/4	1	NM_145058.3	ENSP00000280571.8		Q969X0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246428

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133376

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000690

AC:

AN:

1450066

Hom.:

Cov.:

AF XY:

0.00000970

AC XY:

AN XY:

721558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000905

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Aug 14, 2023

The c.365T>C (p.V122A) alteration is located in exon 2 (coding exon 2) of the RILPL2 gene. This alteration results from a T to C substitution at nucleotide position 365, causing the valine (V) at amino acid position 122 to be replaced by an alanine (A). 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

0.31

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.63

M_CAP

Benign

0.0051

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.4

REVEL

Benign

0.18

Sift

Benign

0.33

Sift4G

Benign

0.80

Polyphen

0.95

Vest4

0.70

MutPred

0.078

Loss of catalytic residue at V122 (P = 0.0246);

MVP

0.39

MPC

0.67

ClinPred

0.60

GERP RS

6.0

Varity_R

0.10

gMVP

0.25

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