Variant 9-136837432-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024718.5(RABL6):c.896C>T(p.Ser299Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000057 in 1,579,570 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

RABL6
NM_024718.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

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:

RABL6 (HGNC:):

RABL6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABL6	NM_024718.5 linkuse as main transcript	c.896C>T	p.Ser299Leu	missense_variant	9/15	ENST00000311502.12	NP_078994.3	Q3YEC7-1
RABL6	NM_001173988.2 linkuse as main transcript	c.899C>T	p.Ser300Leu	missense_variant	9/15		NP_001167459.1	Q3YEC7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL6	ENST00000311502.12 linkuse as main transcript	c.896C>T	p.Ser299Leu	missense_variant	9/15	1	NM_024718.5	ENSP00000311134.7		Q3YEC7-1
RABL6	ENST00000357466.6 linkuse as main transcript	c.896C>T	p.Ser299Leu	missense_variant	9/10	1		ENSP00000350056.2		Q3YEC7-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152202

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000541

AC:

AN:

184820

Hom.:

AF XY:

0.00

AC XY:

AN XY:

101270

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:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000490

AC:

AN:

1427368

Hom.:

Cov.:

AF XY:

0.00000707

AC XY:

AN XY:

707288

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000638

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000845

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

Apr 28, 2022

The c.899C>T (p.S300L) alteration is located in exon 9 (coding exon 9) of the RABL6 gene. This alteration results from a C to T substitution at nucleotide position 899, causing the serine (S) at amino acid position 300 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

0.14

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;.;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Pathogenic

0.51

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Uncertain

2.6

M;.;M;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.7

D;D;D;.

REVEL

Benign

0.26

Sift

Uncertain

0.010

D;D;D;.

Sift4G

Benign

0.094

T;T;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.56

MutPred

0.28

Gain of sheet (P = 0.0028);.;Gain of sheet (P = 0.0028);.;

MVP

0.44

MPC

0.017

ClinPred

0.92

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.59

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