9-136828509-G-C

Position:

• chr9-136828509-G-C

Variant summary

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

The NM_024718.5(RABL6):​c.329G>C​(p.Arg110Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RABL6 NM_024718.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.63

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.329G>C	p.Arg110Pro	missense_variant	4/15	ENST00000311502.12	NP_078994.3
RABL6	NM_001173988.2	c.329G>C	p.Arg110Pro	missense_variant	4/15		NP_001167459.1
RABL6	NM_001173989.4	c.329G>C	p.Arg110Pro	missense_variant	4/8		NP_001167460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABL6	ENST00000311502.12	c.329G>C	p.Arg110Pro	missense_variant	4/15	1	NM_024718.5	ENSP00000311134.7
RABL6	ENST00000357466.6	c.329G>C	p.Arg110Pro	missense_variant	4/10	1		ENSP00000350056.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Jun 10, 2024

The c.329G>C (p.R110P) alteration is located in exon 4 (coding exon 4) of the RABL6 gene. This alteration results from a G to C substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 to be replaced by a proline (P). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.29	N;N;N;N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	D;D;D;D;.
REVEL	Uncertain	0.37
Sift	Benign	0.16	T;D;D;D;.
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		1.0	.;D;D;.;.
Vest4		0.87
MutPred		0.54		Loss of MoRF binding (P = 0.0131);Loss of MoRF binding (P = 0.0131);Loss of MoRF binding (P = 0.0131);Loss of MoRF binding (P = 0.0131);.;
MVP		0.54
MPC		1.3
ClinPred		0.92	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-139722961;