6-143941905-T-G

Position:

chr6-143941905-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001317162.2(PLAGL1):c.911A>C(p.Asn304Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,612,854 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 13 hom. )

Consequence

PLAGL1
NM_001317162.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.89

Variant links:

Genes affected

PLAGL1 (HGNC:9046): (PLAG1 like zinc finger 1) This gene encodes a C2H2 zinc finger protein that functions as a suppressor of cell growth. This gene is often deleted or methylated and silenced in cancer cells. In addition, overexpression of this gene during fetal development is thought to be the causal factor for transient neonatal diabetes mellitus (TNDM). Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding two different protein isoforms. The P1 downstream promoter of this gene is imprinted, with preferential expression from the paternal allele in many tissues. [provided by RefSeq, Nov 2015]

PLAGL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031066835).

BP6

Variant 6-143941905-T-G is Benign according to our data. Variant chr6-143941905-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 780121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 291 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2 linkuse as main transcript	c.911A>C	p.Asn304Thr	missense_variant	8/8	ENST00000674357.1	NP_001304091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357.1 linkuse as main transcript	c.911A>C	p.Asn304Thr	missense_variant	8/8		NM_001317162.2	ENSP00000501459	P1	Q9UM63-1

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

289

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00645

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00305

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00230

AC:

575

AN:

250312

Hom.:

AF XY:

0.00268

AC XY:

363

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00661

Gnomad FIN exome

AF:

0.000423

Gnomad NFE exome

AF:

0.00277

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00328

AC:

4795

AN:

1460792

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

2436

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00615

Gnomad4 FIN exome

AF:

0.000640

Gnomad4 NFE exome

AF:

0.00363

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00191

AC:

291

AN:

152062

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

125

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00687

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00305

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00219

AC:

266

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 14, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PLAGL1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 01, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0010

DANN

Benign

0.74

DEOGEN2

Benign

0.17

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.53

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

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0031

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.20

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

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.023

Sift

Benign

0.13

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

Sift4G

Benign

0.29

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

Polyphen

0.0010

B;B;.;B;B;.;B;B;.;B;B;.;B;.

Vest4

0.071

MVP

0.27

MPC

0.36

ClinPred

0.0095

GERP RS

-8.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.13

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