Variant 6-143941682-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001317162.2(PLAGL1):c.1134G>A(p.Leu378=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,614,194 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 21 hom., cov: 32)

Exomes 𝑓: 0.018 ( 302 hom. )

Consequence

PLAGL1
NM_001317162.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.89

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:

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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 (BayesDel_noAF=-0.48).

BP6

Variant 6-143941682-C-T is Benign according to our data. Variant chr6-143941682-C-T is described in ClinVar as [Benign]. Clinvar id is 3038305.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0145 (2211/152314) while in subpopulation NFE AF= 0.0221 (1501/68018). AF 95% confidence interval is 0.0211. There are 21 homozygotes in gnomad4. There are 1054 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2 linkuse as main transcript	c.1134G>A	p.Leu378=	synonymous_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.1134G>A	p.Leu378=	synonymous_variant	8/8		NM_001317162.2	ENSP00000501459	P1	Q9UM63-1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2215

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0153

AC:

3833

AN:

250456

Hom.:

AF XY:

0.0155

AC XY:

2105

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.00232

Gnomad AMR exome

AF:

0.00896

Gnomad ASJ exome

AF:

0.0212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00389

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0220

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0181

AC:

26427

AN:

1461880

Hom.:

302

Cov.:

AF XY:

0.0180

AC XY:

13083

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.00966

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00431

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0145

AC:

2211

AN:

152314

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1054

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.0221

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0218

EpiControl

AF:

0.0202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLAGL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.1

DANN

Benign

0.74

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