6-143948404-G-C

Variant names:

• chr6-143948404-G-C
• rs2076684
• NM_001317162.2:c.-268C>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.-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
• Publications: 13 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 = 0.432 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.-268C>G		5_prime_UTR	Exon 7 of 8	NP_001304091.1	Q9UM63-1
	PLAGL1	NM_001080951.3		c.-268C>G		5_prime_UTR	Exon 7 of 8	NP_001074420.1	Q9UM63-1
	PLAGL1	NM_001080952.3		c.-268C>G		5_prime_UTR	Exon 6 of 7	NP_001074421.1	Q9UM63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	ENST00000674357.1	MANE Select	c.-268C>G		5_prime_UTR	Exon 7 of 8	ENSP00000501459.1	Q9UM63-1
	PLAGL1	ENST00000354765.6	TSL:1	c.-268C>G		5_prime_UTR	Exon 8 of 9	ENSP00000346810.2	Q9UM63-1
	PLAGL1	ENST00000367571.3	TSL:1	c.-268C>G		5_prime_UTR	Exon 2 of 3	ENSP00000356543.1	Q9UM63-1

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

African (AFR) AF: 0.0830 AC: 695 AN: 8376

American (AMR) AF: 0.131 AC: 1443 AN: 11050

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 825 AN: 8080

East Asian (EAS) AF: 0.442 AC: 7800 AN: 17638

South Asian (SAS) AF: 0.175 AC: 4031 AN: 23032

European-Finnish (FIN) AF: 0.124 AC: 1901 AN: 15320

Middle Eastern (MID) AF: 0.122 AC: 134 AN: 1100

European-Non Finnish (NFE) AF: 0.0930 AC: 13698 AN: 147368

Other (OTH) AF: 0.127 AC: 1900 AN: 14904

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

African (AFR) AF: 0.0825 AC: 3425 AN: 41536

American (AMR) AF: 0.121 AC: 1847 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2314 AN: 5174

South Asian (SAS) AF: 0.192 AC: 924 AN: 4820

European-Finnish (FIN) AF: 0.138 AC: 1457 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6378 AN: 68016

Other (OTH) AF: 0.113 AC: 238 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.68
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: rs2076684; hg19: chr6-144269541; COSMIC: COSV61332614;