Variant 9-136823599-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024718.5(RABL6):c.205G>T(p.Val69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

RABL6
NM_024718.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

RABL6 (HGNC:24703): (RAB, member RAS oncogene family like 6) This gene encodes a member of the Ras superfamily of small GTPases. The encoded protein binds to both GTP and GDP and may play a role in cell growth and survival. Overexpression of this gene may play a role in breast cancer tumorigenesis, and pseudogenes of this gene are located on the long arm of chromosome 2 and the short arm of chromosome 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

RABL6 links:

ENSG00000272679 (HGNC:):

ENSG00000272679 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052918404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABL6	NM_024718.5 linkuse as main transcript	c.205G>T	p.Val69Leu	missense_variant	2/15	ENST00000311502.12	NP_078994.3	Q3YEC7-1
RABL6	NM_001173988.2 linkuse as main transcript	c.205G>T	p.Val69Leu	missense_variant	2/15		NP_001167459.1	Q3YEC7-2
RABL6	NM_001173989.4 linkuse as main transcript	c.205G>T	p.Val69Leu	missense_variant	2/8		NP_001167460.1	Q3YEC7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL6	ENST00000311502.12 linkuse as main transcript	c.205G>T	p.Val69Leu	missense_variant	2/15	1	NM_024718.5	ENSP00000311134.7		Q3YEC7-1
RABL6	ENST00000357466.6 linkuse as main transcript	c.205G>T	p.Val69Leu	missense_variant	2/10	1		ENSP00000350056.2		Q3YEC7-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

247996

Hom.:

AF XY:

0.0000964

AC XY:

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000783

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000649

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:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000661

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

Mar 18, 2024

The c.205G>T (p.V69L) alteration is located in exon 2 (coding exon 2) of the RABL6 gene. This alteration results from a G to T substitution at nucleotide position 205, causing the valine (V) at amino acid position 69 to be replaced by a leucine (L). 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

0.085

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.15

.;T;.;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.72

T;T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.053

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.72

N;N;N;N;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

N;N;N;N;.

REVEL

Benign

0.034

Sift

Benign

0.51

T;T;T;T;.

Sift4G

Benign

0.44

T;T;T;T;T

Polyphen

0.026, 0.021

.;B;B;.;.

Vest4

0.17

MutPred

0.41

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;

MVP

0.43

MPC

0.89

ClinPred

0.058

GERP RS

-0.089

Varity_R

0.039

gMVP

0.58

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