Variant chr12-123485708-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2

The ENST00000376874.9(RILPL1):c.899G>A(p.Arg300Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,448 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RILPL1
ENST00000376874.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

RILPL1 (HGNC:26814): (Rab interacting lysosomal protein like 1) Predicted to enable protein dimerization activity. Predicted to be involved in several processes, including cilium assembly; epithelial cell morphogenesis; and protein transport from ciliary membrane to plasma membrane. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RILPL1 links:

RILPL1 (HGNC:):

RILPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM1

In a mutagenesis_site No loss of interaction with RAB8A. (size 0) in uniprot entity RIPL1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.36796033).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RILPL1	NM_178314.5 linkuse as main transcript	c.899G>A	p.Arg300Gln	missense_variant	5/7	ENST00000376874.9	NP_847884.2	Q5EBL4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RILPL1	ENST00000376874.9 linkuse as main transcript	c.899G>A	p.Arg300Gln	missense_variant	5/7	1	NM_178314.5	ENSP00000366070.4	Q5EBL4-1
RILPL1	ENST00000636882.1 linkuse as main transcript	c.899G>A	p.Arg300Gln	missense_variant	5/8	5		ENSP00000490668.1	A0A1B0GVV3
RILPL1	ENST00000340724.6 linkuse as main transcript	n.1510G>A		non_coding_transcript_exon_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000161

AC:

AN:

248412

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000291

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461270

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

Alfa

AF:

0.0000581

Hom.:

Bravo

AF:

0.0000189

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.899G>A (p.R300Q) alteration is located in exon 5 (coding exon 5) of the RILPL1 gene. This alteration results from a G to A substitution at nucleotide position 899, causing the arginine (R) at amino acid position 300 to be replaced by a glutamine (Q). 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

0.41

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.033

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.18

Sift

Benign

0.11

T;.

Sift4G

Benign

0.22

T;.

Polyphen

0.93

P;.

Vest4

0.86

MVP

0.71

MPC

2.1

ClinPred

0.61

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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