2-129980582-G-A

Position:

• chr2-129980582-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032144.3(RAB6C):​c.467G>A​(p.Arg156Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: RAB6C NM_032144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97

Genes affected

RAB6C (HGNC:16525): (RAB6C, member RAS oncogene family) Enables GTPase activity. Involved in mitotic cell cycle; regulation of centrosome duplication; and response to xenobiotic stimulus. Located in Golgi apparatus and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3409382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB6C	NM_032144.3	c.467G>A	p.Arg156Lys	missense_variant	1/1	ENST00000410061.4	NP_115520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB6C	ENST00000410061.4	c.467G>A	p.Arg156Lys	missense_variant	1/1		NM_032144.3	ENSP00000387307	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

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

Oct 25, 2023

The c.467G>A (p.R156K) alteration is located in exon 1 (coding exon 1) of the RAB6C gene. This alteration results from a G to A substitution at nucleotide position 467, causing the arginine (R) at amino acid position 156 to be replaced by a lysine (K). 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	0.21
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.87
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.93	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.69		Loss of MoRF binding (P = 0.0998);
MVP		0.77
ClinPred		0.46	T
GERP RS		0.65
Varity_R		0.20
gMVP		0.42

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: chr2-130738155;