9-136837363-A-G

Position:

• chr9-136837363-A-G

Variant summary

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

The NM_024718.5(RABL6):​c.827A>G​(p.Glu276Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RABL6 NM_024718.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28

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.827A>G	p.Glu276Gly	missense_variant	9/15	ENST00000311502.12	NP_078994.3
RABL6	NM_001173988.2	c.830A>G	p.Glu277Gly	missense_variant	9/15		NP_001167459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL6	ENST00000311502.12	c.827A>G	p.Glu276Gly	missense_variant	9/15	1	NM_024718.5	ENSP00000311134.7
RABL6	ENST00000357466.6	c.827A>G	p.Glu276Gly	missense_variant	9/10	1		ENSP00000350056.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.830A>G (p.E277G) alteration is located in exon 9 (coding exon 9) of the RABL6 gene. This alteration results from a A to G substitution at nucleotide position 830, causing the glutamic acid (E) at amino acid position 277 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Uncertain	0.032	D
MutationAssessor	Uncertain	2.5	M;.;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.5	D;D;D;.
REVEL	Benign	0.20
Sift	Benign	0.20	T;T;T;.
Sift4G	Benign	0.15	T;T;D;T
Polyphen		0.96	D;D;.;.
Vest4		0.65
MutPred		0.28		Gain of sheet (P = 0.0085);.;Gain of sheet (P = 0.0085);.;
MVP		0.39
MPC		0.020
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.39
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr9-139731815;