chr4-13376553-G-T

Variant names:

• chr4-13376553-G-T
• rs786200944
• NM_001017979.3:c.565C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001017979.3(RAB28):​c.565C>A​(p.Gln189Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB28 NM_001017979.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.02

Genes affected

RAB28 (HGNC:9768): (RAB28, member RAS oncogene family) This gene encodes a member of the Rab subfamily of Ras-related small GTPases. The encoded protein may be involved in regulating intracellular trafficking. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 9 and X. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB28	NM_001017979.3	c.565C>A	p.Gln189Lys	missense_variant	Exon 6 of 7	ENST00000330852.10	NP_001017979.1
RAB28	NM_004249.4	c.565C>A	p.Gln189Lys	missense_variant	Exon 6 of 8	ENST00000288723.9	NP_004240.2
RAB28	NM_001159601.2	c.565C>A	p.Gln189Lys	missense_variant	Exon 6 of 8		NP_001153073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB28	ENST00000330852.10	c.565C>A	p.Gln189Lys	missense_variant	Exon 6 of 7	1	NM_001017979.3	ENSP00000328551.5
RAB28	ENST00000288723.9	c.565C>A	p.Gln189Lys	missense_variant	Exon 6 of 8	1	NM_004249.4	ENSP00000288723.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Benign	0.81
DEOGEN2	Benign	0.047	T;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.90	T;T;T
Polyphen		0.33	B;P;.
Vest4		0.68
MutPred		0.37		Gain of ubiquitination at Q189 (P = 0.0162);Gain of ubiquitination at Q189 (P = 0.0162);Gain of ubiquitination at Q189 (P = 0.0162);
MVP		0.85
MPC		0.28
ClinPred		0.77	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs786200944; hg19: chr4-13378177;