RAB28 p.Cys217Cys

Variant names:

• chr4-13369887-A-A
• NM_004249.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-13369888--
• chr4-13369888-A-G

Variant summary

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

The NM_004249.4(RAB28):​c. variant causes a exon region change. 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_004249.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• Publications: 0 publications found

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]

RAB28 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• RAB28-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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_004249.4. 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
	RAB28	NM_004249.4	MANE Plus Clinical	c.		exon_region	Exon 7 of 8	NP_004240.2	P51157-2
	RAB28	NM_001017979.3	MANE Select	c.		intron	N/A	NP_001017979.1	P51157-1
	RAB28	NM_001159601.2		c.		intron	N/A	NP_001153073.1	P51157-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB28	ENST00000288723.9	TSL:1 MANE Plus Clinical	c.		exon_region	Exon 7 of 8	ENSP00000288723.4	P51157-2
	RAB28	ENST00000330852.10	TSL:1 MANE Select	c.		intron	N/A	ENSP00000328551.5	P51157-1
	RAB28	ENST00000508274.5	TSL:1	n.		intron	N/A	ENSP00000424043.1	Q8WVF3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-13371511;