rs2268443

Variant names:

• chr6-143951103-A-G
• rs2268443
• NM_001317162.2:c.-324-2643T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-143951103-A-G
• chr6-143951103-A-T

Variant summary

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

The NM_006718.5(PLAGL1):​c.-324-2643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 146,902 control chromosomes in the GnomAD database, including 19,878 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 0.48 (19878 hom., cov: 32)
• Consequence: PLAGL1 NM_006718.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006718.5. 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.-324-2643T>C		intron	N/A	NP_001304091.1
	PLAGL1	NM_001080951.3		c.-324-2643T>C		intron	N/A	NP_001074420.1
	PLAGL1	NM_001080952.3		c.-324-2643T>C		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.-324-2643T>C		intron	N/A	ENSP00000501459.1
	PLAGL1	ENST00000354765.6	TSL:1	c.-324-2643T>C		intron	N/A	ENSP00000346810.2
	PLAGL1	ENST00000367571.3	TSL:1	c.-324-2643T>C		intron	N/A	ENSP00000356543.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 70255 AN: 146784 Hom.: 19821 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.438

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.479 AC: 70371 AN: 146902 Hom.: 19878 Cov.: 32 AF XY: 0.486 AC XY: 34870 AN XY: 71740

African (AFR) AF: 0.793 AC: 32553 AN: 41036

American (AMR) AF: 0.512 AC: 7480 AN: 14620

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1030 AN: 3296

East Asian (EAS) AF: 0.640 AC: 3246 AN: 5074

South Asian (SAS) AF: 0.414 AC: 1922 AN: 4642

European-Finnish (FIN) AF: 0.391 AC: 3812 AN: 9752

Middle Eastern (MID) AF: 0.444 AC: 127 AN: 286

European-Non Finnish (NFE) AF: 0.291 AC: 19037 AN: 65318

Other (OTH) AF: 0.445 AC: 897 AN: 2014

Alfa AF: 0.342 Hom.: 8797

Bravo AF: 0.489

Asia WGS AF: 0.498 AC: 1732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		2.3
Mutation Taster		=99/1	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: rs2268443; hg19: chr6-144272240;