13-27920088-A-ACTCCCGG

Position:

• chr13-27920088-A-ACTCCCGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000209.4(PDX1):​c.-29_-23dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,546,314 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: PDX1 NM_000209.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.235

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDX1	NM_000209.4	c.-29_-23dup		5_prime_UTR_variant	1/2	ENST00000381033.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDX1	ENST00000381033.5	c.-29_-23dup		5_prime_UTR_variant	1/2	1	NM_000209.4	P1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 151638 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000197 AC: 28 AN: 142004 Hom.: 0 AF XY: 0.000234 AC XY: 18 AN XY: 76988

Gnomad AFR exome AF: 0.000161

Gnomad AMR exome AF: 0.0000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000284

Gnomad SAS exome AF: 0.000447

Gnomad FIN exome AF: 0.000197

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000177 AC: 247 AN: 1394564 Hom.: 0 Cov.: 32 AF XY: 0.000198 AC XY: 136 AN XY: 687812

Gnomad4 AFR exome AF: 0.000381

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.000147

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.000190

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151750 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74148

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maturity-onset diabetes of the young type 4 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing;curation

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 18, 2011

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193922352; hg19: chr13-28494225;