6-143970013-G-T

Variant names:

• chr6-143970013-G-T
• rs13218225
• NM_001317162.2:c.-543-1035C>A

Variant summary

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

The NM_001317162.2(PLAGL1):​c.-543-1035C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 152,130 control chromosomes in the GnomAD database, including 786 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 0.090 (786 hom., cov: 31)
• Consequence: PLAGL1 NM_001317162.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	NM_001317162.2	MANE Select	c.-543-1035C>A		intron	N/A	NP_001304091.1
	PLAGL1	NM_001080951.3		c.-575-1035C>A		intron	N/A	NP_001074420.1
	PLAGL1	NM_001080952.3		c.-589-1035C>A		intron	N/A	NP_001074421.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	ENST00000674357.1	MANE Select	c.-543-1035C>A		intron	N/A	ENSP00000501459.1
	PLAGL1	ENST00000354765.6	TSL:1	c.-792-1035C>A		intron	N/A	ENSP00000346810.2
	PLAGL1	ENST00000416623.5	TSL:1	c.-396-1035C>A		intron	N/A	ENSP00000400060.1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13681 AN: 152012 Hom.: 788 Cov.: 31

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0941

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.0899 AC: 13677 AN: 152130 Hom.: 786 Cov.: 31 AF XY: 0.0862 AC XY: 6405 AN XY: 74346

African (AFR) AF: 0.0265 AC: 1102 AN: 41544

American (AMR) AF: 0.0941 AC: 1437 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0941 AC: 326 AN: 3466

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0324 AC: 156 AN: 4822

European-Finnish (FIN) AF: 0.0795 AC: 840 AN: 10570

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9471 AN: 67956

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.122 Hom.: 2296

Bravo AF: 0.0876

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.38
PhyloP100		-0.22
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: rs13218225; hg19: chr6-144291150;