Genetic Variant PLAGL1:c.-268C>G (chr6-143948404-G-C) – 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.-268C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 399,098 control chromosomes in the GnomAD database, including 4,638 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 0.11 ( 1342 hom., cov: 32)

Exomes 𝑓: 0.13 ( 3296 hom. )

Consequence

PLAGL1
NM_001317162.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.679

Publications

13 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAGL1	NM_001317162.2 link	c.-268C>G		5_prime_UTR_variant	Exon 7 of 8	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.-268C>G		5_prime_UTR_variant	Exon 7 of 8		NM_001317162.2	ENSP00000501459.1		Q9UM63-1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17113

AN:

152112

Hom.:

1343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0938

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.131

AC:

32427

AN:

246868

Hom.:

3296

Cov.:

AF XY:

0.133

AC XY:

17204

AN XY:

129092

show subpopulations

African (AFR)

AF:

0.0830

AC:

695

AN:

8376

American (AMR)

AF:

0.131

AC:

1443

AN:

11050

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

825

AN:

8080

East Asian (EAS)

AF:

0.442

AC:

7800

AN:

17638

South Asian (SAS)

AF:

0.175

AC:

4031

AN:

23032

European-Finnish (FIN)

AF:

0.124

AC:

1901

AN:

15320

Middle Eastern (MID)

AF:

0.122

AC:

134

AN:

1100

European-Non Finnish (NFE)

AF:

0.0930

AC:

13698

AN:

147368

Other (OTH)

AF:

0.127

AC:

1900

AN:

14904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1225

2449

3674

4898

6123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.112

AC:

17123

AN:

152230

Hom.:

1342

Cov.:

AF XY:

0.118

AC XY:

8774

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0825

AC:

3425

AN:

41536

American (AMR)

AF:

0.121

AC:

1847

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0968

AC:

336

AN:

3472

East Asian (EAS)

AF:

0.447

AC:

2314

AN:

5174

South Asian (SAS)

AF:

0.192

AC:

924

AN:

4820

European-Finnish (FIN)

AF:

0.138

AC:

1457

AN:

10594

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0938

AC:

6378

AN:

68016

Other (OTH)

AF:

0.113

AC:

238

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

755

1510

2264

3019

3774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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:

0.0450

Hom.:

Bravo

AF:

0.112

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.68

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over