rs193922352

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_000209.4(PDX1):​c.-36_-23delCTCCCGGCTCCCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,546,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

PDX1
NM_000209.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.941
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000198 (30/151638) while in subpopulation NFE AF= 0.000339 (23/67896). AF 95% confidence interval is 0.000231. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDX1NM_000209.4 linkc.-36_-23delCTCCCGGCTCCCGG 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.-36_-23delCTCCCGGCTCCCGG 5_prime_UTR_variant Exon 1 of 2 1 NM_000209.4 ENSP00000370421.4 P52945

Frequencies

GnomAD3 genomes
AF:
0.000198
AC:
30
AN:
151638
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000485
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000475
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000339
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000120
AC:
17
AN:
142004
Hom.:
0
AF XY:
0.000117
AC XY:
9
AN XY:
76988
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000820
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000894
Gnomad FIN exome
AF:
0.000329
Gnomad NFE exome
AF:
0.000157
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000267
AC:
373
AN:
1394556
Hom.:
0
AF XY:
0.000259
AC XY:
178
AN XY:
687812
show subpopulations
Gnomad4 AFR exome
AF:
0.000127
Gnomad4 AMR exome
AF:
0.0000841
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000758
Gnomad4 FIN exome
AF:
0.000230
Gnomad4 NFE exome
AF:
0.000312
Gnomad4 OTH exome
AF:
0.000208
GnomAD4 genome
AF:
0.000198
AC:
30
AN:
151638
Hom.:
0
Cov.:
33
AF XY:
0.000243
AC XY:
18
AN XY:
74026
show subpopulations
Gnomad4 AFR
AF:
0.0000485
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000475
Gnomad4 NFE
AF:
0.000339
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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