Variant chr4-39505308-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_003359.4(UGDH):c.1100A>G(p.Tyr367Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UGDH
NM_003359.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 7.45

Variant links:

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]

UGDH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.946

PP5

Variant 4-39505308-T-C is Pathogenic according to our data. Variant chr4-39505308-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 810646.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGDH	NM_003359.4 linkuse as main transcript	c.1100A>G	p.Tyr367Cys	missense_variant	9/12	ENST00000316423.11
UGDH	NM_001184700.2 linkuse as main transcript	c.899A>G	p.Tyr300Cys	missense_variant	8/11
UGDH	NM_001184701.2 linkuse as main transcript	c.809A>G	p.Tyr270Cys	missense_variant	8/11
UGDH	XM_005262667.4 linkuse as main transcript	c.1139A>G	p.Tyr380Cys	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGDH	ENST00000316423.11 linkuse as main transcript	c.1100A>G	p.Tyr367Cys	missense_variant	9/12	1	NM_003359.4	P1	O60701-1
UGDH	ENST00000506179.5 linkuse as main transcript	c.1100A>G	p.Tyr367Cys	missense_variant	9/12	5		P1	O60701-1
UGDH	ENST00000501493.6 linkuse as main transcript	c.899A>G	p.Tyr300Cys	missense_variant	8/11	2			O60701-2
UGDH	ENST00000507089.5 linkuse as main transcript	c.809A>G	p.Tyr270Cys	missense_variant	8/11	2			O60701-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1449644

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

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

- -

Developmental and epileptic encephalopathy, 84

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 07, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;.;D;.

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.95

D;D;D;D

MetaSVM

Uncertain

0.65

MutationAssessor

Pathogenic

3.2

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-8.5

D;D;D;D

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.95

MutPred

0.72

Loss of catalytic residue at Y367 (P = 0.0206);.;Loss of catalytic residue at Y367 (P = 0.0206);.;

MVP

0.97

MPC

1.0

ClinPred

1.0

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.95

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over