Variant chr9-136837420-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_024718.5(RABL6):c.884C>T(p.Pro295Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000423 in 1,585,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

RABL6
NM_024718.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

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:

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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=0.096874595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABL6	NM_024718.5 link	c.884C>T	p.Pro295Leu	missense_variant	9/15	ENST00000311502.12	NP_078994.3	Q3YEC7-1
RABL6	NM_001173988.2 link	c.887C>T	p.Pro296Leu	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 link	c.884C>T	p.Pro295Leu	missense_variant	9/15	1	NM_024718.5	ENSP00000311134.7		Q3YEC7-1
RABL6	ENST00000357466.6 link	c.884C>T	p.Pro295Leu	missense_variant	9/10	1		ENSP00000350056.2		Q3YEC7-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152198

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:

0.0000441

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

192144

Hom.:

AF XY:

0.0000380

AC XY:

AN XY:

105368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000774

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000243

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000433

AC:

AN:

1432838

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

710460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000485

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000491

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

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:

0.0000441

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000337

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Dec 27, 2023

The c.887C>T (p.P296L) 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 887, causing the proline (P) at amino acid position 296 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

0.087

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.017

T;.;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.61

T;T;D;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.097

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;.;N;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.68

N;N;N;.

REVEL

Benign

0.12

Sift

Benign

0.061

T;T;D;.

Sift4G

Benign

0.10

T;T;D;T

Polyphen

0.082

B;B;.;.

Vest4

0.24

MutPred

0.15

Loss of glycosylation at P295 (P = 0.0122);.;Loss of glycosylation at P295 (P = 0.0122);.;

MVP

0.10

MPC

0.0075

ClinPred

0.062

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

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