13-27920029-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000209.4(PDX1):c.-106del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,345,708 control chromosomes in the GnomAD database, including 37,586 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4301 hom., cov: 27)
  • Exomes 𝑓: 0.23 (33285 hom.)
• Consequence: PDX1 NM_000209.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.786

Genes affected

PDX1 (HGNC:6107): (pancreatic and duodenal homeobox 1) The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (IDDM), as well as maturity onset diabetes of the young type 4 (MODY4). [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-27920029-AG-A is Benign according to our data. Variant chr13-27920029-AG-A is described in ClinVar as [Benign]. Clinvar id is 1179450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDX1	NM_000209.4	c.-106del		5_prime_UTR_variant	1/2	ENST00000381033.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDX1	ENST00000381033.5	c.-106del		5_prime_UTR_variant	1/2	1	NM_000209.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34618 AN: 152062 Hom.: 4297 Cov.: 27

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.228 AC: 271783 AN: 1193528 Hom.: 33285 Cov.: 9 AF XY: 0.226 AC XY: 135045 AN XY: 596986

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.228 AC: 34631 AN: 152180 Hom.: 4301 Cov.: 27 AF XY: 0.233 AC XY: 17312 AN XY: 74384

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.247

Alfa AF: 0.226 Hom.: 493

Bravo AF: 0.234

Asia WGS AF: 0.269 AC: 935 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 18, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs146021107; hg19: chr13-28494166;