Variant 12-123533452-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_178314.5(RILPL1):c.31G>A(p.Ala11Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000019 in 1,529,296 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

RILPL1
NM_178314.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08609125).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RILPL1	NM_178314.5 linkuse as main transcript	c.31G>A	p.Ala11Thr	missense_variant	1/7	ENST00000376874.9	NP_847884.2
RILPL1	NM_001319243.2 linkuse as main transcript	c.31G>A	p.Ala11Thr	missense_variant	1/8		NP_001306172.1
RILPL1	XM_047428787.1 linkuse as main transcript	c.31G>A	p.Ala11Thr	missense_variant	1/7		XP_047284743.1
RILPL1	XM_047428788.1 linkuse as main transcript	c.31G>A	p.Ala11Thr	missense_variant	1/3		XP_047284744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RILPL1	ENST00000376874.9 linkuse as main transcript	c.31G>A	p.Ala11Thr	missense_variant	1/7	1	NM_178314.5	ENSP00000366070	P3	Q5EBL4-1
RILPL1	ENST00000636882.1 linkuse as main transcript	c.31G>A	p.Ala11Thr	missense_variant	1/8	5		ENSP00000490668	A1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000516

AC:

AN:

135752

Hom.:

AF XY:

0.0000678

AC XY:

AN XY:

73800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000283

Gnomad SAS exome

AF:

0.000181

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1377272

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

676230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000570

Gnomad4 SAS exome

AF:

0.000216

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.0000526

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000160

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

Jul 19, 2023

The c.31G>A (p.A11T) alteration is located in exon 1 (coding exon 1) of the RILPL1 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.095

Eigen_PC

Benign

0.023

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.32

N;.

REVEL

Benign

0.037

Sift

Uncertain

0.012

D;.

Sift4G

Benign

0.36

T;.

Polyphen

0.32

B;.

Vest4

0.30

MutPred

0.17

Gain of glycosylation at A11 (P = 0.0227);Gain of glycosylation at A11 (P = 0.0227);

MVP

0.081

MPC

1.2

ClinPred

0.11

GERP RS

3.2

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.15

gMVP

0.75

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