Variant 22-50782204-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001130919.3(RABL2B):c.91G>A(p.Ala31Thr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000097 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RABL2B
NM_001130919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

RABL2B (HGNC:9800): (RAB, member of RAS oncogene family like 2B) The RABL2B protein is a member of the RAB gene family which belongs to the RAS GTPase superfamily. RABL2B is located within a subtelomeric region of 22q13.3. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

RABL2B links:

RPL23AP7 (HGNC:):

RPL23AP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4170216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABL2B	NM_001130919.3 linkuse as main transcript	c.91G>A	p.Ala31Thr	missense_variant	2/9	ENST00000691320.1
RPL23AP82	NR_026981.1 linkuse as main transcript	n.242-916C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABL2B	ENST00000691320.1 linkuse as main transcript	c.91G>A	p.Ala31Thr	missense_variant	2/9		NM_001130919.3	A2	Q9UNT1-2
RPL23AP7	ENST00000496652.5 linkuse as main transcript	n.380-916C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149476

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

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:

0.0000444

Gnomad OTH

AF:

0.000504

GnomAD3 exomes

AF:

0.0000852

AC:

AN:

199526

Hom.:

AF XY:

0.0000841

AC XY:

AN XY:

107064

show subpopulations

Gnomad AFR exome

AF:

0.000230

Gnomad AMR exome

AF:

0.0000345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000594

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000966

AC:

135

AN:

1397440

Hom.:

Cov.:

AF XY:

0.0000951

AC XY:

AN XY:

694058

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

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:

0.000118

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000114

AC:

AN:

149476

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

72754

show subpopulations

Gnomad4 AFR

AF:

0.000273

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000444

Gnomad4 OTH

AF:

0.000504

Alfa

AF:

0.000192

Hom.:

ExAC

AF:

0.0000918

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

Nov 22, 2022

The c.91G>A (p.A31T) alteration is located in exon 3 (coding exon 1) of the RABL2B gene. This alteration results from a G to A substitution at nucleotide position 91, causing the alanine (A) at amino acid position 31 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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;.;.;T;T;.;.

Eigen

Uncertain

0.37

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.90

D;.;D;.;D;D;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.42

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.060

MutationAssessor

Uncertain

2.1

M;M;M;M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;N

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0040

D;D;D;D;D;D;D

Sift4G

Uncertain

0.039

D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D;.

Vest4

0.44

MVP

0.78

ClinPred

0.66

GERP RS

1.2

Varity_R

0.28

gMVP

0.43

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