Genetic Variant RASL11B:p.Arg31Ser (chr4-52862598-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_023940.3(RASL11B):c.91C>A(p.Arg31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RASL11B
NM_023940.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11

Variant links:

Genes affected

RASL11B (HGNC:23804): (RAS like family 11 member B) Predicted to enable G protein activity; GTP binding activity; and transforming growth factor beta receptor binding activity. Predicted to act upstream of or within negative regulation of transforming growth factor beta receptor signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

RASL11B links:

LINC01618 (HGNC:27195): (long intergenic non-protein coding RNA 1618)

LINC01618 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=0.08833623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL11B	NM_023940.3 link	c.91C>A	p.Arg31Ser	missense_variant	Exon 1 of 4	ENST00000248706.5	NP_076429.1	Q9BPW5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RASL11B	ENST00000248706.5 link	c.91C>A	p.Arg31Ser	missense_variant	Exon 1 of 4	1	NM_023940.3	ENSP00000248706.3	Q9BPW5
RASL11B	ENST00000515677.1 link	n.267C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
LINC01618	ENST00000650700.1 link	n.989-670C>A		intron_variant	Intron 8 of 10
LINC01618	ENST00000652441.1 link	n.504-670C>A		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719598

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91C>A (p.R31S) alteration is located in exon 1 (coding exon 1) of the RASL11B gene. This alteration results from a C to A substitution at nucleotide position 91, causing the arginine (R) at amino acid position 31 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0092

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.65

M_CAP

Benign

0.034

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.35

REVEL

Benign

0.18

Sift

Benign

0.70

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.35

MutPred

0.47

Loss of MoRF binding (P = 0.025);

MVP

0.58

MPC

0.44

ClinPred

0.20

GERP RS

5.1

Varity_R

0.22

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over