NM_017817.3:c.565A>G

Variant names:

• chr13-110523805-T-C
• rs1884377018
• NM_017817.3:c.565A>G

Variant summary

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

The NM_017817.3(RAB20):​c.565A>G​(p.Asn189Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N189S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RAB20 NM_017817.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72
• Publications: 0 publications found

Genes affected

RAB20 (HGNC:18260): (RAB20, member RAS oncogene family) Predicted to enable GTPase activity. Involved in phagosome acidification and phagosome-lysosome fusion. Located in Golgi apparatus and phagocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

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_017817.3. 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
	RAB20	NM_017817.3	MANE Select	c.565A>G	p.Asn189Asp	missense	Exon 2 of 2	NP_060287.1	Q9NX57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB20	ENST00000267328.5	TSL:1 MANE Select	c.565A>G	p.Asn189Asp	missense	Exon 2 of 2	ENSP00000267328.3	Q9NX57
	RAB20	ENST00000907762.1		c.565A>G	p.Asn189Asp	missense	Exon 3 of 3	ENSP00000577821.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	1.9	M
PhyloP100		4.7
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.57
Sift	Benign	0.091	T
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.78		Gain of catalytic residue at L192 (P = 0.0058)
MVP		0.79
MPC		1.4
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.43
gMVP		0.77
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1884377018; hg19: chr13-111176152;