17-28715651-TC-CT

Variant names:

• chr17-28715651-TC-CT
• NM_031934.6:c.368_369delGAinsAG
• RAB34 p.Arg123Lys

Variant summary

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

The NM_031934.6(RAB34):​c.368_369delGAinsAG​(p.Arg123Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAB34 NM_031934.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• Publications: 0 publications found

Genes affected

RAB34 (HGNC:16519): (RAB34, member RAS oncogene family) This gene encodes a protein belonging to the RAB family of proteins, which are small GTPases involved in protein transport. This family member is a Golgi-bound member of the secretory pathway that is involved in the repositioning of lysosomes and the activation of macropinocytosis. Alternative splicing of this gene results in multiple transcript variants. An alternatively spliced transcript variant produces the nine-amino acid residue-repeats (NARR) protein, which is a functionally distinct nucleolar protein resulting from a different reading frame. [provided by RefSeq, Dec 2016]

RAB34 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome 20

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031934.6. 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
	RAB34	NM_031934.6	MANE Select	c.368_369delGAinsAG	p.Arg123Lys	missense	N/A	NP_114140.4
	RAB34	NM_001144943.1		c.539_540delGAinsAG	p.Arg180Lys	missense	N/A	NP_001138415.1	B4DNC0
	RAB34	NM_001142624.2		c.539_540delGAinsAG	p.Arg180Lys	missense	N/A	NP_001136096.2	B4DNC0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB34	ENST00000395245.9	TSL:1 MANE Select	c.368_369delGAinsAG	p.Arg123Lys	missense	N/A	ENSP00000378666.3	Q9BZG1-1
	RAB34	ENST00000453384.7	TSL:1	c.542_543delGAinsAG	p.Arg181Lys	missense	N/A	ENSP00000413156.3	E7ES60
	RAB34	ENST00000301043.10	TSL:1	c.368_369delGAinsAG	p.Arg123Lys	missense	N/A	ENSP00000301043.6	Q9BZG1-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

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: chr17-27042669;