Variant 6-143941563-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001317162.2(PLAGL1):c.1253T>A(p.Leu418Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000145 in 1,589,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PLAGL1
NM_001317162.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.080308884).

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2 linkuse as main transcript	c.1253T>A	p.Leu418Gln	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.1253T>A	p.Leu418Gln	missense_variant	8/8		NM_001317162.2	ENSP00000501459	P1	Q9UM63-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000864

AC:

AN:

231590

Hom.:

AF XY:

0.0000803

AC XY:

AN XY:

124460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1437394

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

711936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000507

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.1253T>A (p.L418Q) alteration is located in exon 7 (coding exon 2) of the PLAGL1 gene. This alteration results from a T to A substitution at nucleotide position 1253, causing the leucine (L) at amino acid position 418 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

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

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.67

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

M_CAP

Benign

0.017

MetaRNN

Benign

0.080

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

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

MutationTaster

Benign

0.89

D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.15

Sift

Benign

0.052

T;.;.;T;T;D;T;.;D;.;.;.;T;.

Sift4G

Uncertain

0.0090

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

Polyphen

0.99

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

Vest4

0.53

MutPred

0.10

Loss of catalytic residue at L418 (P = 0.0106);Loss of catalytic residue at L418 (P = 0.0106);.;Loss of catalytic residue at L418 (P = 0.0106);Loss of catalytic residue at L418 (P = 0.0106);.;Loss of catalytic residue at L418 (P = 0.0106);Loss of catalytic residue at L418 (P = 0.0106);.;Loss of catalytic residue at L418 (P = 0.0106);Loss of catalytic residue at L418 (P = 0.0106);.;Loss of catalytic residue at L418 (P = 0.0106);.;

MVP

0.22

MPC

0.38

ClinPred

0.14

GERP RS

4.3

Varity_R

0.086

gMVP

0.45

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