Variant rs193922359 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PM4_SupportingBP6

The NM_000209.4(PDX1):c.726_728del(p.Pro244del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,381,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PDX1
NM_000209.4 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43

Variant links:

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]

PDX1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000209.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 13-27924562-TGCC-T is Benign according to our data. Variant chr13-27924562-TGCC-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDX1	NM_000209.4 linkuse as main transcript	c.726_728del	p.Pro244del	inframe_deletion	2/2	ENST00000381033.5	NP_000200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDX1	ENST00000381033.5 linkuse as main transcript	c.726_728del	p.Pro244del	inframe_deletion	2/2	1	NM_000209.4	ENSP00000370421	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000224

AC:

AN:

1381368

Hom.:

AF XY:

0.0000308

AC XY:

AN XY:

681984

show subpopulations

Gnomad4 AFR exome

AF:

0.0000685

Gnomad4 AMR exome

AF:

0.0000293

Gnomad4 ASJ exome

AF:

0.0000424

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000260

Gnomad4 FIN exome

AF:

0.0000228

Gnomad4 NFE exome

AF:

0.0000223

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing