Variant 22-50777956-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001130919.3(RABL2B):c.133G>A(p.Gly45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RABL2B
NM_001130919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

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:

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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=0.19615206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABL2B	NM_001130919.3 linkuse as main transcript	c.133G>A	p.Gly45Ser	missense_variant	3/9	ENST00000691320.1	NP_001124391.1
RPL23AP82	NR_026981.1 linkuse as main transcript	n.242-5164C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL2B	ENST00000691320.1 linkuse as main transcript	c.133G>A	p.Gly45Ser	missense_variant	3/9		NM_001130919.3	ENSP00000509250	A2	Q9UNT1-2
RPL23AP7	ENST00000496652.5 linkuse as main transcript	n.380-5164C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 12, 2024

The c.133G>A (p.G45S) alteration is located in exon 4 (coding exon 2) of the RABL2B gene. This alteration results from a G to A substitution at nucleotide position 133, causing the glycine (G) at amino acid position 45 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

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

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

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

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

M_CAP

Benign

0.032

MetaRNN

Benign

0.20

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

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.69

N;N;N;N;.;N;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.2

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

REVEL

Benign

0.16

Sift

Benign

0.32

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

Sift4G

Benign

0.60

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

Polyphen

0.63

P;P;B;P;.;P;.

Vest4

0.27

MutPred

0.26

Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);Gain of disorder (P = 0.0826);

MVP

0.36

ClinPred

0.17

GERP RS

1.9

Varity_R

0.093

gMVP

0.44

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