chr17-42130364-G-GA

Variant names:

• chr17-42130364-G-GA
• NM_004583.4:c.138dupT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004583.4(RAB5C):​c.138dupT​(p.His47SerfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB5C NM_004583.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.925
• Publications: 0 publications found

Genes affected

RAB5C (HGNC:9785): (RAB5C, member RAS oncogene family) Members of the Rab protein family are small GTPases of the Ras superfamily that are thought to ensure fidelity in the process of docking and/or fusion of vesicles with their correct acceptor compartment (Han et al., 1996 [PubMed 8646882]).[supplied by OMIM, Nov 2010]

ENSG00000267261 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5C	NM_004583.4	MANE Select	c.138dupT	p.His47SerfsTer21	frameshift	Exon 2 of 6	NP_004574.2
	RAB5C	NM_001252039.2		c.237dupT	p.His80SerfsTer21	frameshift	Exon 3 of 7	NP_001238968.1	P51148-2
	RAB5C	NM_201434.3		c.138dupT	p.His47SerfsTer21	frameshift	Exon 3 of 7	NP_958842.1	P51148-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5C	ENST00000346213.9	TSL:1 MANE Select	c.138dupT	p.His47SerfsTer21	frameshift	Exon 2 of 6	ENSP00000345689.5	P51148-1
	ENSG00000267261	ENST00000592574.1	TSL:5	c.138dupT	p.His47SerfsTer21	frameshift	Exon 2 of 8	ENSP00000468367.1	K7ERQ8
	RAB5C	ENST00000547517.5	TSL:1	c.237dupT	p.His80SerfsTer21	frameshift	Exon 3 of 7	ENSP00000447053.1	P51148-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-40282382;