rs782559570

Variant names:

• chr17-42125841-C-A
• NM_004583.4:c.593G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-42125841-C-A
• chr17-42125841-C-T

Variant summary

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

The NM_004583.4(RAB5C):​c.593G>T​(p.Arg198Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R198Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RAB5C NM_004583.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06

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

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=0.29369527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB5C	NM_004583.4	c.593G>T	p.Arg198Leu	missense_variant	Exon 6 of 6	ENST00000346213.9	NP_004574.2
RAB5C	NM_001252039.2	c.692G>T	p.Arg231Leu	missense_variant	Exon 7 of 7		NP_001238968.1
RAB5C	NM_201434.3	c.593G>T	p.Arg198Leu	missense_variant	Exon 7 of 7		NP_958842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB5C	ENST00000346213.9	c.593G>T	p.Arg198Leu	missense_variant	Exon 6 of 6	1	NM_004583.4	ENSP00000345689.5
ENSG00000267261	ENST00000592574.1	c.441+2420G>T		intron_variant	Intron 4 of 7	5		ENSP00000468367.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459576 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725740

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;T;.
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.094	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.98	D;D;.
Vest4		0.46
MutPred		0.33		Loss of methylation at R198 (P = 0.0707);Loss of methylation at R198 (P = 0.0707);.;
MVP		0.75
MPC		0.93
ClinPred		0.86	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr17-40277859;