rs9403542

Variant names:

• chr6-143984431-T-C
• rs9403542
• NM_001317162.2:c.-544+704A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-143984431-T-C
• chr6-143984431-T-G

Variant summary

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

The NM_001317162.2(PLAGL1):​c.-544+704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,922 control chromosomes in the GnomAD database, including 22,818 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 0.53 (22818 hom., cov: 31)
• Consequence: PLAGL1 NM_001317162.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 9 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317162.2. 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.-544+704A>G		intron	N/A	NP_001304091.1	Q9UM63-1
	PLAGL1	NM_001080951.3		c.-576+704A>G		intron	N/A	NP_001074420.1	Q9UM63-1
	PLAGL1	NM_001080952.3		c.-589-15453A>G		intron	N/A	NP_001074421.1	Q9UM63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	ENST00000674357.1	MANE Select	c.-544+704A>G		intron	N/A	ENSP00000501459.1	Q9UM63-1
	PLAGL1	ENST00000354765.6	TSL:1	c.-793+704A>G		intron	N/A	ENSP00000346810.2	Q9UM63-1
	PLAGL1	ENST00000416623.5	TSL:1	c.-396-15453A>G		intron	N/A	ENSP00000400060.1	Q9UM63-1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80134 AN: 151804 Hom.: 22817 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80151 AN: 151922 Hom.: 22818 Cov.: 31 AF XY: 0.527 AC XY: 39105 AN XY: 74230

African (AFR) AF: 0.310 AC: 12851 AN: 41432

American (AMR) AF: 0.468 AC: 7139 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3466

East Asian (EAS) AF: 0.720 AC: 3717 AN: 5162

South Asian (SAS) AF: 0.681 AC: 3271 AN: 4804

European-Finnish (FIN) AF: 0.578 AC: 6091 AN: 10544

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43142 AN: 67938

Other (OTH) AF: 0.551 AC: 1164 AN: 2114

Alfa AF: 0.602 Hom.: 119198

Bravo AF: 0.509

Asia WGS AF: 0.696 AC: 2417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.82
PhyloP100		-0.54
Mutation Taster		=100/0	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: rs9403542; hg19: chr6-144305568;