chr19-56812972-C-T

Position:

• chr19-56812972-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006210.3(PEG3):​c.*703G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 985,208 control chromosomes in the GnomAD database, including 307,082 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47506 hom., cov: 32)
  • Exomes 𝑓: 0.79 (259576 hom.)
• Consequence: PEG3 NM_006210.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

Genes affected

PEG3 (HGNC:8826): (paternally expressed 3) In human, ZIM2 and PEG3 are treated as two distinct genes though they share multiple 5' exons and a common promoter and both genes are paternally expressed (PMID:15203203). Alternative splicing events connect their shared 5' exons either with the remaining 4 exons unique to ZIM2, or with the remaining 2 exons unique to PEG3. In contrast, in other mammals ZIM2 does not undergo imprinting and, in mouse, cow, and likely other mammals as well, the ZIM2 and PEG3 genes do not share exons. Human PEG3 protein belongs to the Kruppel C2H2-type zinc finger protein family. PEG3 may play a role in cell proliferation and p53-mediated apoptosis. PEG3 has also shown tumor suppressor activity and tumorigenesis in glioma and ovarian cells. Alternative splicing of this PEG3 gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2009]

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]

PEG3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEG3	NM_006210.3	c.*703G>A		3_prime_UTR_variant	10/10	ENST00000326441.15	NP_006201.1
ZIM2	NM_001387356.1	c.490+4774G>A		intron_variant		ENST00000629319.3	NP_001374285.1
PEG3-AS1	NR_023847.2	n.493C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEG3	ENST00000326441.15	c.*703G>A		3_prime_UTR_variant	10/10	1	NM_006210.3	ENSP00000326581	P1
ZIM2	ENST00000629319.3	c.490+4774G>A		intron_variant		5	NM_001387356.1	ENSP00000486502	A2
	ENST00000652504.1	n.844+2744C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119987 AN: 151982 Hom.: 47458 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.795

GnomAD4 exome AF: 0.789 AC: 657556 AN: 833108 Hom.: 259576 Cov.: 31 AF XY: 0.789 AC XY: 303701 AN XY: 384788

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.848

Gnomad4 ASJ exome AF: 0.817

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.848

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome AF: 0.790 AC: 120095 AN: 152100 Hom.: 47506 Cov.: 32 AF XY: 0.791 AC XY: 58813 AN XY: 74356

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.799

Alfa AF: 0.788 Hom.: 74505

Bravo AF: 0.792

Asia WGS AF: 0.781 AC: 2713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.8
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1055359; hg19: chr19-57324340; COSMIC: COSV55652554; COSMIC: COSV55652554;