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
NM_000209.4 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.235
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]
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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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 151638Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
22
AN:
151638
Hom.:
Cov.:
33
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GnomAD2 exomes AF: 0.000197 AC: 28AN: 142004 AF XY: 0.000234 show subpopulations
GnomAD2 exomes
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AC:
28
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142004
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GnomAD4 exome AF: 0.000177 AC: 247AN: 1394564Hom.: 0 Cov.: 32 AF XY: 0.000198 AC XY: 136AN XY: 687812 show subpopulations
GnomAD4 exome
AF:
AC:
247
AN:
1394564
Hom.:
Cov.:
32
AF XY:
AC XY:
136
AN XY:
687812
Gnomad4 AFR exome
AF:
AC:
12
AN:
31496
Gnomad4 AMR exome
AF:
AC:
1
AN:
35672
Gnomad4 ASJ exome
AF:
AC:
0
AN:
25130
Gnomad4 EAS exome
AF:
AC:
10
AN:
35686
Gnomad4 SAS exome
AF:
AC:
33
AN:
79110
Gnomad4 FIN exome
AF:
AC:
7
AN:
47740
Gnomad4 NFE exome
AF:
AC:
171
AN:
1077084
Gnomad4 Remaining exome
AF:
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
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Age
GnomAD4 genome AF: 0.000145 AC: 22AN: 151750Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74148 show subpopulations
GnomAD4 genome
AF:
AC:
22
AN:
151750
Hom.:
Cov.:
33
AF XY:
AC XY:
11
AN XY:
74148
Gnomad4 AFR
AF:
AC:
0.000241838
AN:
0.000241838
Gnomad4 AMR
AF:
AC:
0.0000654793
AN:
0.0000654793
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
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AC:
0
AN:
0
Gnomad4 SAS
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AC:
0
AN:
0
Gnomad4 FIN
AF:
AC:
0.000189861
AN:
0.000189861
Gnomad4 NFE
AF:
AC:
0.000132571
AN:
0.000132571
Gnomad4 OTH
AF:
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
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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
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mutation Taster
=299/1
polymorphism
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at