Variant 6-143942001-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001317162.2(PLAGL1):c.815C>T(p.Ala272Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,593,688 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 16 hom. )

Consequence

PLAGL1
NM_001317162.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003219813).

BP6

Variant 6-143942001-G-A is Benign according to our data. Variant chr6-143942001-G-A is described in ClinVar as [Benign]. Clinvar id is 771407.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1604/152250) while in subpopulation AFR AF= 0.0356 (1479/41548). AF 95% confidence interval is 0.0341. There are 31 homozygotes in gnomad4. There are 745 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1604 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2 linkuse as main transcript	c.815C>T	p.Ala272Val	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.815C>T	p.Ala272Val	missense_variant	8/8		NM_001317162.2	ENSP00000501459	P1	Q9UM63-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1604

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00312

AC:

728

AN:

233204

Hom.:

AF XY:

0.00249

AC XY:

311

AN XY:

124844

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.000983

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000302

Gnomad OTH exome

AF:

0.00303

GnomAD4 exome

AF:

0.00117

AC:

1681

AN:

1441438

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

745

AN XY:

714522

show subpopulations

Gnomad4 AFR exome

AF:

0.0364

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.00279

GnomAD4 genome

AF:

0.0105

AC:

1604

AN:

152250

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

745

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0356

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00208

Hom.:

Bravo

AF:

0.0122

ESP6500AA

AF:

0.0368

AC:

162

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00334

AC:

406

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.49

DANN

Benign

0.58

DEOGEN2

Benign

0.098

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.47

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

MetaRNN

Benign

0.0032

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

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

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

0.21

PROVEAN

Benign

-0.32

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

REVEL

Benign

0.031

Sift

Benign

0.47

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

Sift4G

Benign

0.35

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

Polyphen

0.017

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

Vest4

0.051

MVP

0.38

MPC

0.35

ClinPred

0.0013

GERP RS

-2.5

Varity_R

0.017

gMVP

0.14

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