13-27920088-ACTCCCGGCTCCCGG-ACTCCCGG

Variant names:

• chr13-27920088-ACTCCCGG-A
• rs193922352
• NM_000209.4:c.-29_-23delCTCCCGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000209.4(PDX1):​c.-29_-23delCTCCCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000585 in 1,546,280 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (3 hom.)
• Consequence: PDX1 NM_000209.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.941

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 13-27920088-ACTCCCGG-A is Benign according to our data. Variant chr13-27920088-ACTCCCGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 422562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000494 (75/151748) while in subpopulation NFE AF= 0.000619 (42/67886). AF 95% confidence interval is 0.00047. There are 0 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDX1	NM_000209.4	c.-29_-23delCTCCCGG		5_prime_UTR_variant	Exon 1 of 2	ENST00000381033.5	NP_000200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDX1	ENST00000381033	c.-29_-23delCTCCCGG		5_prime_UTR_variant	Exon 1 of 2	1	NM_000209.4	ENSP00000370421.4

Frequencies

GnomAD3 genomes AF: 0.000481 AC: 73 AN: 151636 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000619

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000465 AC: 66 AN: 142004 Hom.: 2 AF XY: 0.000351 AC XY: 27 AN XY: 76988

Gnomad AFR exome AF: 0.000322

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.000122

Gnomad EAS exome AF: 0.000379

Gnomad SAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000864

Gnomad OTH exome AF: 0.000722

GnomAD4 exome AF: 0.000594 AC: 829 AN: 1394532 Hom.: 3 AF XY: 0.000587 AC XY: 404 AN XY: 687796

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.000279

Gnomad4 EAS exome AF: 0.000673

Gnomad4 SAS exome AF: 0.000480

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000617

Gnomad4 OTH exome AF: 0.000796

GnomAD4 genome AF: 0.000494 AC: 75 AN: 151748 Hom.: 0 Cov.: 33 AF XY: 0.000486 AC XY: 36 AN XY: 74146

Gnomad4 AFR AF: 0.000556

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000619

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000620

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 01, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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;