17-42125805-C-G

Variant names:

• chr17-42125805-C-G
• rs1366208306
• NM_004583.4:c.629G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004583.4(RAB5C):​c.629G>C​(p.Arg210Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R210Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RAB5C NM_004583.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15951782).

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.629G>C	p.Arg210Pro	missense	Exon 6 of 6	NP_004574.2
	RAB5C	NM_001252039.2		c.728G>C	p.Arg243Pro	missense	Exon 7 of 7	NP_001238968.1	P51148-2
	RAB5C	NM_201434.3		c.629G>C	p.Arg210Pro	missense	Exon 7 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.629G>C	p.Arg210Pro	missense	Exon 6 of 6	ENSP00000345689.5	P51148-1
	RAB5C	ENST00000547517.5	TSL:1	c.728G>C	p.Arg243Pro	missense	Exon 7 of 7	ENSP00000447053.1	P51148-2
	RAB5C	ENST00000393860.7	TSL:1	c.629G>C	p.Arg210Pro	missense	Exon 7 of 7	ENSP00000377440.3	P51148-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0058	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.34
Sift	Benign	0.071	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.30
MutPred		0.24		Gain of glycosylation at R210 (P = 0.0458)
MVP		0.67
MPC		0.85
ClinPred		0.67	D
GERP RS		4.0
Varity_R		0.71
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs1366208306; hg19: chr17-40277823;