Variant 13-27920053-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000209.4(PDX1):c.-86G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,493,422 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 25 hom. )

Consequence

PDX1
NM_000209.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 13-27920053-G-T is Benign according to our data. Variant chr13-27920053-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00945 (1439/152322) while in subpopulation AFR AF= 0.0236 (981/41578). AF 95% confidence interval is 0.0224. There are 17 homozygotes in gnomad4. There are 687 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDX1	NM_000209.4 linkuse as main transcript	c.-86G>T		5_prime_UTR_variant	1/2	ENST00000381033.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDX1	ENST00000381033.5 linkuse as main transcript	c.-86G>T		5_prime_UTR_variant	1/2	1	NM_000209.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00936

AC:

1425

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00367

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.00450

AC:

6030

AN:

1341100

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

2991

AN XY:

664016

show subpopulations

Gnomad4 AFR exome

AF:

0.0241

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00307

Gnomad4 EAS exome

AF:

0.000537

Gnomad4 SAS exome

AF:

0.00570

Gnomad4 FIN exome

AF:

0.00719

Gnomad4 NFE exome

AF:

0.00389

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.00945

AC:

1439

AN:

152322

Hom.:

Cov.:

AF XY:

0.00922

AC XY:

687

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0236

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.00414

Gnomad4 NFE

AF:

0.00368

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00688

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over