dbSNP rs9373409: PLAGL1:c.-431+77G>A (chr6-143966081-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001317162.2(PLAGL1):c.-431+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,052 control chromosomes in the GnomAD database, including 10,187 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10182 hom., cov: 32)

Exomes 𝑓: 0.47 ( 5 hom. )

Consequence

PLAGL1
NM_001317162.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.438

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

transient neonatal diabetes mellitus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PLAGL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAGL1	NM_001317162.2 link	c.-431+77G>A		intron_variant	Intron 4 of 7	ENST00000674357.1	NP_001304091.1	Q9UM63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357.1 link	c.-431+77G>A		intron_variant	Intron 4 of 7		NM_001317162.2	ENSP00000501459.1		Q9UM63-1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54514

AN:

151904

Hom.:

10189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.379

GnomAD4 exome

AF:

0.467

AC:

AN:

Hom.:

Cov.:

AF XY:

0.538

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.542

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.359

AC:

54520

AN:

152022

Hom.:

10182

Cov.:

AF XY:

0.350

AC XY:

25973

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.284

AC:

11789

AN:

41456

American (AMR)

AF:

0.309

AC:

4721

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1361

AN:

3472

East Asian (EAS)

AF:

0.297

AC:

1536

AN:

5170

South Asian (SAS)

AF:

0.370

AC:

1784

AN:

4818

European-Finnish (FIN)

AF:

0.272

AC:

2876

AN:

10560

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.430

AC:

29246

AN:

67958

Other (OTH)

AF:

0.378

AC:

800

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1759

3518

5277

7036

8795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.409

Hom.:

54355

Bravo

AF:

0.358

Asia WGS

AF:

0.335

AC:

1166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.4

(source)

DANN

Benign

0.73

PhyloP100

-0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over