6-143970013-G-T

Position:

• chr6-143970013-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2	c.-543-1035C>A		intron_variant		ENST00000674357.1	NP_001304091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357.1	c.-543-1035C>A		intron_variant			NM_001317162.2	ENSP00000501459	P1

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

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.0941

Gnomad4 ASJ AF: 0.0941

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0795

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.127 Hom.: 1771

Bravo AF: 0.0876

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.38

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: rs13218225; hg19: chr6-144291150;