rs1049846

Variant names:

• chr6-143940343-C-T
• rs1049846
• NM_001317162.2:c.*1081G>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.*1081G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,916 control chromosomes in the GnomAD database, including 9,842 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 0.36 (9842 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PLAGL1 NM_001317162.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• 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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 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.*1081G>A		3_prime_UTR	Exon 8 of 8	NP_001304091.1
	PLAGL1	NM_001080951.3		c.*1081G>A		3_prime_UTR	Exon 8 of 8	NP_001074420.1
	PLAGL1	NM_001080952.3		c.*1081G>A		3_prime_UTR	Exon 7 of 7	NP_001074421.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	ENST00000674357.1	MANE Select	c.*1081G>A		3_prime_UTR	Exon 8 of 8	ENSP00000501459.1
	PLAGL1	ENST00000354765.6	TSL:1	c.*1081G>A		3_prime_UTR	Exon 9 of 9	ENSP00000346810.2
	PLAGL1	ENST00000416623.5	TSL:1	c.*1081G>A		3_prime_UTR	Exon 4 of 4	ENSP00000400060.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54178 AN: 151798 Hom.: 9837 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.334

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.357 AC: 54234 AN: 151916 Hom.: 9842 Cov.: 33 AF XY: 0.356 AC XY: 26415 AN XY: 74234

African (AFR) AF: 0.395 AC: 16351 AN: 41382

American (AMR) AF: 0.391 AC: 5978 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1252 AN: 5182

South Asian (SAS) AF: 0.461 AC: 2226 AN: 4828

European-Finnish (FIN) AF: 0.272 AC: 2861 AN: 10504

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23574 AN: 67962

Other (OTH) AF: 0.337 AC: 710 AN: 2104

Alfa AF: 0.349 Hom.: 37852

Bravo AF: 0.358

Asia WGS AF: 0.366 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.49
PhyloP100		-0.17
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: rs1049846; hg19: chr6-144261480;