rs9373409

chr6-143966081-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PLAGL1	NM_001317162.2	c.-431+77G>A		intron_variant		ENST00000674357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAGL1	ENST00000674357.1	c.-431+77G>A		intron_variant			NM_001317162.2	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54514 AN: 151904 Hom.: 10189 Cov.: 32

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: 14 AN: 30 Hom.: 5 Cov.: 0 AF XY: 0.538 AC XY: 14 AN XY: 26

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.359 AC: 54520 AN: 152022 Hom.: 10182 Cov.: 32 AF XY: 0.350 AC XY: 25973 AN XY: 74288

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.378

Alfa AF: 0.417 Hom.: 27000

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
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs9373409; hg19: chr6-144287218;