13-27920121-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000209.4(PDX1):​c.-18C>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 0.000986 in 1,549,406 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 5 hom. )

Consequence

PDX1
NM_000209.4 5_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.135
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 13-27920121-C-T is Benign according to our data. Variant chr13-27920121-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 36402.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00492 (750/152348) while in subpopulation AFR AF= 0.0161 (671/41588). AF 95% confidence interval is 0.0151. There are 4 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDX1NM_000209.4 linkuse as main transcriptc.-18C>T 5_prime_UTR_variant 1/2 ENST00000381033.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDX1ENST00000381033.5 linkuse as main transcriptc.-18C>T 5_prime_UTR_variant 1/21 NM_000209.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00491
AC:
748
AN:
152232
Hom.:
4
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0161
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00379
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00122
AC:
176
AN:
144478
Hom.:
0
AF XY:
0.00106
AC XY:
83
AN XY:
78214
show subpopulations
Gnomad AFR exome
AF:
0.0195
Gnomad AMR exome
AF:
0.00135
Gnomad ASJ exome
AF:
0.000121
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000446
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000190
Gnomad OTH exome
AF:
0.000952
GnomAD4 exome
AF:
0.000556
AC:
777
AN:
1397058
Hom.:
5
Cov.:
33
AF XY:
0.000495
AC XY:
341
AN XY:
689014
show subpopulations
Gnomad4 AFR exome
AF:
0.0182
Gnomad4 AMR exome
AF:
0.00163
Gnomad4 ASJ exome
AF:
0.000477
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000631
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000389
Gnomad4 OTH exome
AF:
0.00140
GnomAD4 genome
AF:
0.00492
AC:
750
AN:
152348
Hom.:
4
Cov.:
33
AF XY:
0.00542
AC XY:
404
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0161
Gnomad4 AMR
AF:
0.00379
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00231
Hom.:
1
Bravo
AF:
0.00565

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 14, 2017This 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. -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsMar 25, 2021- -
Maturity-onset diabetes of the young type 4 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testing;curationWomen's Health and Genetics/Laboratory Corporation of America, LabCorpAug 18, 2011- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
11
DANN
Benign
0.94

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.

Other links and lift over

dbSNP: rs193922351; hg19: chr13-28494258; API