rs9373409

Variant names:

• chr6-143966081-C-T
• rs9373409
• NM_001317162.2:c.-431+77G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001289045.2(PLAGL1):​c.-662G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 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_001289045.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 18 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289045.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	NM_001317162.2	MANE Select	c.-431+77G>A		intron	N/A	NP_001304091.1
	PLAGL1	NM_001289045.2		c.-662G>A		5_prime_UTR	Exon 3 of 7	NP_001275974.1
	PLAGL1	NM_001080951.3		c.-431+77G>A		intron	N/A	NP_001074420.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	ENST00000674357.1	MANE Select	c.-431+77G>A		intron	N/A	ENSP00000501459.1
	PLAGL1	ENST00000354765.6	TSL:1	c.-593+77G>A		intron	N/A	ENSP00000346810.2
	PLAGL1	ENST00000416623.5	TSL:1	c.-325+2826G>A		intron	N/A	ENSP00000400060.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.542 AC: 13 AN: 24

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.4
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)

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

Other links and lift over

dbSNP: rs9373409; hg19: chr6-144287218;