16-627581-CCC-ACA

Variant names:

• chr16-627581-CCC-ACA
• NM_021168.5:c.805_807delCCCinsACA
• RAB40C p.Pro269Thr

Variant summary

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

The NM_021168.5(RAB40C):​c.805_807delCCCinsACA​(p.Pro269Thr) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P269S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RAB40C NM_021168.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

Genes affected

RAB40C (HGNC:18285): (RAB40C, member RAS oncogene family) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in protein localization to plasma membrane. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in endosome; plasma membrane; and synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021168.5. 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
	RAB40C	NM_021168.5	MANE Select	c.805_807delCCCinsACA	p.Pro269Thr	missense	N/A	NP_066991.3
	RAB40C	NM_001172663.2		c.805_807delCCCinsACA	p.Pro269Thr	missense	N/A	NP_001166134.1	Q96S21-1
	RAB40C	NM_001172664.2		c.805_807delCCCinsACA	p.Pro269Thr	missense	N/A	NP_001166135.1	Q96S21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB40C	ENST00000248139.8	TSL:1 MANE Select	c.805_807delCCCinsACA	p.Pro269Thr	missense	N/A	ENSP00000248139.3	Q96S21-1
	RAB40C	ENST00000851113.1		c.985_987delCCCinsACA	p.Pro329Thr	missense	N/A	ENSP00000521172.1
	RAB40C	ENST00000851112.1		c.817_819delCCCinsACA	p.Pro273Thr	missense	N/A	ENSP00000521171.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

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: chr16-677581;