17-28357686-CTT-GTG

Variant names:

• chr17-28357686-CTT-GTG
• NM_152464.3:c.16_18delCTTinsGTG
• VMA12 p.Leu6Val

Variant summary

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

The NM_152464.3(VMA12):​c.16_18delCTTinsGTG​(p.Leu6Val) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L6F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VMA12 NM_152464.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 0 publications found

Genes affected

VMA12 (HGNC:18085): (transmembrane protein 199) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) in some human cells. The encoded protein shares some homology with the yeast protein Vma12. Defects in this gene are a cause of congenital disorder of glycosylation, type IIp. [provided by RefSeq, Mar 2016]

ENSG00000258924 (HGNC:):

POLDIP2 (HGNC:23781): (DNA polymerase delta interacting protein 2) This gene encodes a protein that interacts with the DNA polymerase delta p50 subunit, as well as with proliferating cell nuclear antigen. The encoded protein maybe play a role in the ability of the replication fork to bypass DNA lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152464.3. 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
	VMA12	NM_152464.3	MANE Select	c.16_18delCTTinsGTG	p.Leu6Val	missense	N/A	NP_689677.1	Q8N511
	POLDIP2	NM_015584.5	MANE Select	c.-240_-238delAAGinsCAC		upstream_gene	N/A	NP_056399.1	Q9Y2S7
	POLDIP2	NM_001290145.2		c.-240_-238delAAGinsCAC		upstream_gene	N/A	NP_001277074.1	B4DEM9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMA12	ENST00000292114.8	TSL:1 MANE Select	c.16_18delCTTinsGTG	p.Leu6Val	missense	N/A	ENSP00000292114.3	Q8N511
	VMA12	ENST00000971958.1		c.16_18delCTTinsGTG	p.Leu6Val	missense	N/A	ENSP00000642017.1
	VMA12	ENST00000555264.6	TSL:5	n.16_18delCTTinsGTG		non_coding_transcript_exon	Exon 1 of 7	ENSP00000462356.1	J3KS81

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		0.57

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: chr17-26684709;