9-136837378-G-A

Position:

• chr9-136837378-G-A

Variant summary

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

The NM_024718.5(RABL6):​c.842G>A​(p.Gly281Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RABL6 NM_024718.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.22

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 (HGNC:):

ACMG classification

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	c.842G>A	p.Gly281Asp	missense_variant	9/15	ENST00000311502.12	NP_078994.3
RABL6	NM_001173988.2	c.845G>A	p.Gly282Asp	missense_variant	9/15		NP_001167459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL6	ENST00000311502.12	c.842G>A	p.Gly281Asp	missense_variant	9/15	1	NM_024718.5	ENSP00000311134.7
RABL6	ENST00000357466.6	c.842G>A	p.Gly281Asp	missense_variant	9/10	1		ENSP00000350056.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1450858 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720906

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Meniere disease Uncertain:1

Uncertain significance, no assertion criteria provided

research

Center for Computational Biology & Bioinformatics, University of California, San Diego

Jun 03, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.6	M;.;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.6	D;D;D;.
REVEL	Benign	0.23
Sift	Benign	0.049	D;D;D;.
Sift4G	Benign	0.066	T;D;T;T
Polyphen		0.98	D;D;.;.
Vest4		0.63
MutPred		0.32		Gain of helix (P = 0.0034);.;Gain of helix (P = 0.0034);.;
MVP		0.43
MPC		0.0097
ClinPred		0.91	D
GERP RS		4.3
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8
Varity_R		0.33
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139731830;