6-143948404-G-C

Position:

• chr6-143948404-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317162.2(PLAGL1):​c.-268C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 399,098 control chromosomes in the GnomAD database, including 4,638 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 0.11 (1342 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3296 hom.)
• Consequence: PLAGL1 NM_001317162.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2	c.-268C>G		5_prime_UTR_variant	7/8	ENST00000674357.1	NP_001304091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357.1	c.-268C>G		5_prime_UTR_variant	7/8		NM_001317162.2	ENSP00000501459	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17113 AN: 152112 Hom.: 1343 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.131 AC: 32427 AN: 246868 Hom.: 3296 Cov.: 0 AF XY: 0.133 AC XY: 17204 AN XY: 129092

Gnomad4 AFR exome AF: 0.0830

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.112 AC: 17123 AN: 152230 Hom.: 1342 Cov.: 32 AF XY: 0.118 AC XY: 8774 AN XY: 74424

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0938

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0450 Hom.: 38

Bravo AF: 0.112

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.79

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: rs2076684; hg19: chr6-144269541; COSMIC: COSV61332614;