19-56812972-C-T

Variant names:

• chr19-56812972-C-T
• rs1055359
• NM_006210.3:c.*703G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ENSG00000286125 (HGNC:):

PEG3-AS1 (HGNC:35127): (PEG3 antisense RNA 1) This gene is located in the paternally expressed gene 3 (PEG3) imprinted region on chromosome 19. The corresponding transcript in mouse is imprinted and regulates expression of the mouse Peg3 gene. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEG3	NM_006210.3	c.*703G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000326441.15	NP_006201.1
ZIM2	NM_001387356.1	c.490+4774G>A		intron_variant	Intron 9 of 12	ENST00000629319.3	NP_001374285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEG3	ENST00000326441.15	c.*703G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_006210.3	ENSP00000326581.7
ZIM2	ENST00000629319.3	c.490+4774G>A		intron_variant	Intron 9 of 12	5	NM_001387356.1	ENSP00000486502.2

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

African (AFR) AF: 0.784 AC: 12369 AN: 15778

American (AMR) AF: 0.848 AC: 834 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 4209 AN: 5152

East Asian (EAS) AF: 0.668 AC: 2421 AN: 3624

South Asian (SAS) AF: 0.848 AC: 13946 AN: 16452

European-Finnish (FIN) AF: 0.785 AC: 548 AN: 698

Middle Eastern (MID) AF: 0.792 AC: 1281 AN: 1618

European-Non Finnish (NFE) AF: 0.788 AC: 600366 AN: 761512

Other (OTH) AF: 0.791 AC: 21582 AN: 27290

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

African (AFR) AF: 0.785 AC: 32547 AN: 41482

American (AMR) AF: 0.824 AC: 12598 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2840 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3495 AN: 5164

South Asian (SAS) AF: 0.847 AC: 4089 AN: 4828

European-Finnish (FIN) AF: 0.779 AC: 8228 AN: 10560

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53708 AN: 67984

Other (OTH) AF: 0.799 AC: 1687 AN: 2112

Alfa AF: 0.789 Hom.: 175233

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
PhyloP100		0.058
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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