chr22-23160905-CGC-TGT

Variant names:

• chr22-23160905-CGC-TGT
• NM_004914.5:c.646_648delCGCinsTGT
• RAB36 p.Arg216Cys

Variant summary

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

The NM_004914.5(RAB36):​c.646_648delCGCinsTGT​(p.Arg216Cys) variant causes a missense change. 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: 34)
• Consequence: RAB36 NM_004914.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18
• Publications: 0 publications found

Genes affected

RAB36 (HGNC:9775): (RAB36, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in protein transport. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004914.5. 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
	RAB36	NM_004914.5	MANE Select	c.646_648delCGCinsTGT	p.Arg216Cys	missense	N/A	NP_004905.3
	RAB36	NM_001349877.1		c.916_918delCGCinsTGT	p.Arg306Cys	missense	N/A	NP_001336806.1
	RAB36	NM_001349878.1		c.824_826delCGCinsTGT	p.ProArg275LeuCys	missense	N/A	NP_001336807.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB36	ENST00000263116.8	TSL:1 MANE Select	c.646_648delCGCinsTGT	p.Arg216Cys	missense	N/A	ENSP00000263116.3	O95755-1
	RAB36	ENST00000341989.9	TSL:1	c.580_582delCGCinsTGT	p.Arg194Cys	missense	N/A	ENSP00000343494.5	O95755-2
	RAB36	ENST00000857885.1		c.646_648delCGCinsTGT	p.Arg216Cys	missense	N/A	ENSP00000527944.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

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: chr22-23503092;