19-56782026-ACT-GCG

Variant names:

• chr19-56782026-ACT-GCG
• NM_001387356.1:c.664_666delAGTinsCGC
• ZIM2 p.Ser222Arg

Variant summary

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

The NM_001387356.1(ZIM2):​c.664_666delAGTinsCGC​(p.Ser222Arg) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZIM2 NM_001387356.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 0 publications found

Genes affected

ZIM2 (HGNC:12875): (zinc finger imprinted 2) In human, ZIM2 and PEG3 (GeneID:5178) are two distinct genes that share a set of 5' exons and have a common promoter, and both genes are paternally expressed. Alternative splicing events connect the shared exons either with the remaining 4 exons unique to ZIM2, or with the remaining 2 exons unique to PEG3. This is in contrast to mouse and cow, where ZIM2 and PEG3 genes do not share exons in common, and the imprinting status of ZIM2 is also not conserved amongst mammals. Additional 5' alternatively spliced transcripts encoding the same protein have been found for the human ZIM2 gene. [provided by RefSeq, Oct 2010]

ENSG00000286125 (HGNC:):

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387356.1. 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
	ZIM2	NM_001387356.1	MANE Select	c.664_666delAGTinsCGC	p.Ser222Arg	missense	N/A	NP_001374285.1	A0A8I5KWX0
	ZIM2	NM_001369773.1		c.664_666delAGTinsCGC	p.Ser222Arg	missense	N/A	NP_001356702.1	A0A8I5KWX0
	ZIM2	NM_001369774.1		c.664_666delAGTinsCGC	p.Ser222Arg	missense	N/A	NP_001356703.1	A0A8I5KWX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIM2	ENST00000629319.3	TSL:5 MANE Select	c.664_666delAGTinsCGC	p.Ser222Arg	missense	N/A	ENSP00000486502.2	A0A8I5KWX0
	ZIM2	ENST00000593711.6	TSL:1	c.571_573delAGTinsCGC	p.Ser191Arg	missense	N/A	ENSP00000472306.1	Q9NZV7
	ZIM2	ENST00000601070.5	TSL:1	c.571_573delAGTinsCGC	p.Ser191Arg	missense	N/A	ENSP00000470326.1	Q9NZV7

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		-0.42

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: chr19-57293394;