19-56814177-G-C

Position:

chr19-56814177-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006210.3(PEG3):c.4265C>G(p.Ala1422Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,614,070 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 43 hom. )

Consequence

PEG3
NM_006210.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.809

Variant links:

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]

PEG3 links:

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]

ZIM2 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005486667).

BP6

Variant 19-56814177-G-C is Benign according to our data. Variant chr19-56814177-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 777915.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEG3	NM_006210.3 linkuse as main transcript	c.4265C>G	p.Ala1422Gly	missense_variant	10/10	ENST00000326441.15	NP_006201.1
ZIM2	NM_001387356.1 linkuse as main transcript	c.490+3569C>G		intron_variant		ENST00000629319.3	NP_001374285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEG3	ENST00000326441.15 linkuse as main transcript	c.4265C>G	p.Ala1422Gly	missense_variant	10/10	1	NM_006210.3	ENSP00000326581	P1	Q9GZU2-1
ZIM2	ENST00000629319.3 linkuse as main transcript	c.490+3569C>G		intron_variant		5	NM_001387356.1	ENSP00000486502	A2
	ENST00000652504.1 linkuse as main transcript	n.844+3949G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

564

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00617

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00417

AC:

1046

AN:

251082

Hom.:

AF XY:

0.00434

AC XY:

589

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00434

Gnomad FIN exome

AF:

0.000741

Gnomad NFE exome

AF:

0.00642

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00674

AC:

9855

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

4898

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00367

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00443

Gnomad4 FIN exome

AF:

0.000731

Gnomad4 NFE exome

AF:

0.00794

Gnomad4 OTH exome

AF:

0.00563

GnomAD4 genome

AF:

0.00370

AC:

564

AN:

152250

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00617

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00616

Hom.:

Bravo

AF:

0.00422

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00413

AC:

501

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00676

EpiControl

AF:

0.00646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.;.;.;.;.;.;.;.;.;T;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.85

.;.;.;.;.;.;.;.;T;T;T;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0055

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

M;.;.;.;.;.;.;.;.;.;.;M;M

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.6

N;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.070

Sift

Uncertain

0.017

D;.;.;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.078

T;.;.;.;.;.;.;.;.;T;T;T;T

Polyphen

0.80

P;.;.;.;.;.;.;.;.;.;.;P;P

Vest4

0.25

MVP

0.66

MPC

0.32

ClinPred

0.042

GERP RS

4.2

Varity_R

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over