4-39505748-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3PP5
The NM_003359.4(UGDH):c.907G>A(p.Val303Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,014 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Consequence
UGDH
NM_003359.4 missense, splice_region
NM_003359.4 missense, splice_region
Scores
3
10
5
Splicing: ADA: 0.9994
2
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
UGDH (HGNC:12525): (UDP-glucose 6-dehydrogenase) The protein encoded by this gene converts UDP-glucose to UDP-glucuronate and thereby participates in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated compounds are common components of the extracellular matrix and likely play roles in signal transduction, cell migration, and cancer growth and metastasis. The expression of this gene is up-regulated by transforming growth factor beta and down-regulated by hypoxia. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a helix (size 27) in uniprot entity UGDH_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_003359.4
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
PP5
Variant 4-39505748-C-T is Pathogenic according to our data. Variant chr4-39505748-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 810649.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UGDH | NM_003359.4 | c.907G>A | p.Val303Ile | missense_variant, splice_region_variant | 8/12 | ENST00000316423.11 | |
UGDH | NM_001184700.2 | c.706G>A | p.Val236Ile | missense_variant, splice_region_variant | 7/11 | ||
UGDH | NM_001184701.2 | c.616G>A | p.Val206Ile | missense_variant, splice_region_variant | 7/11 | ||
UGDH | XM_005262667.4 | c.946G>A | p.Val316Ile | missense_variant, splice_region_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UGDH | ENST00000316423.11 | c.907G>A | p.Val303Ile | missense_variant, splice_region_variant | 8/12 | 1 | NM_003359.4 | P1 | |
UGDH | ENST00000506179.5 | c.907G>A | p.Val303Ile | missense_variant, splice_region_variant | 8/12 | 5 | P1 | ||
UGDH | ENST00000501493.6 | c.706G>A | p.Val236Ile | missense_variant, splice_region_variant | 7/11 | 2 | |||
UGDH | ENST00000507089.5 | c.616G>A | p.Val206Ile | missense_variant, splice_region_variant | 7/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 31
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74274
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Epileptic encephalopathy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Section for Clinical Neurogenetics, University of Tübingen | Oct 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;D;T;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at