13-27920088-A-ACTCCCGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_000209.4(PDX1):​c.-29_-23dupCTCCCGG 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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.235
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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000145 (22/151750) while in subpopulation AFR AF = 0.000242 (10/41350). AF 95% confidence interval is 0.000131. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDX1NM_000209.4 linkc.-29_-23dupCTCCCGG 5_prime_UTR_variant Exon 1 of 2 ENST00000381033.5 NP_000200.1 P52945

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDX1ENST00000381033 linkc.-29_-23dupCTCCCGG 5_prime_UTR_variant Exon 1 of 2 1 NM_000209.4 ENSP00000370421.4 P52945

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
151638
Hom.:
0
Cov.:
33
show subpopulations
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
GnomAD2 exomes
AF:
0.000197
AC:
28
AN:
142004
AF XY:
0.000234
show subpopulations
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 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
show subpopulations
Gnomad4 AFR exome
AF:
0.000381
AC:
12
AN:
31496
Gnomad4 AMR exome
AF:
0.0000280
AC:
1
AN:
35672
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
25130
Gnomad4 EAS exome
AF:
0.000280
AC:
10
AN:
35686
Gnomad4 SAS exome
AF:
0.000417
AC:
33
AN:
79110
Gnomad4 FIN exome
AF:
0.000147
AC:
7
AN:
47740
Gnomad4 NFE exome
AF:
0.000159
AC:
171
AN:
1077084
Gnomad4 Remaining exome
AF:
0.000190
AC:
11
AN:
57798
Heterozygous variant carriers
0
15
30
45
60
75
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
151750
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74148
show subpopulations
Gnomad4 AFR
AF:
0.000242
AC:
0.000241838
AN:
0.000241838
Gnomad4 AMR
AF:
0.0000655
AC:
0.0000654793
AN:
0.0000654793
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.000190
AC:
0.000189861
AN:
0.000189861
Gnomad4 NFE
AF:
0.000133
AC:
0.000132571
AN:
0.000132571
Gnomad4 OTH
AF:
0.00
AC:
0
AN:
0
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Maturity-onset diabetes of the young type 4 Uncertain:1
Aug 18, 2011
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing;curation

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Mutation Taster
=299/1
polymorphism

Splicing

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: rs193922352; hg19: chr13-28494225; API