4-39504452-C-A

Position:

chr4-39504452-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_003359.4(UGDH):c.1228G>T(p.Ala410Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,012 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UGDH
NM_003359.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.49

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 Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

PP5

Variant 4-39504452-C-A is Pathogenic according to our data. Variant chr4-39504452-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 810644.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGDH	NM_003359.4 linkuse as main transcript	c.1228G>T	p.Ala410Ser	missense_variant	10/12	ENST00000316423.11	NP_003350.1	O60701-1
UGDH	NM_001184700.2 linkuse as main transcript	c.1027G>T	p.Ala343Ser	missense_variant	9/11		NP_001171629.1	O60701-2
UGDH	NM_001184701.2 linkuse as main transcript	c.937G>T	p.Ala313Ser	missense_variant	9/11		NP_001171630.1	O60701-3
UGDH	XM_005262667.4 linkuse as main transcript	c.1267G>T	p.Ala423Ser	missense_variant	10/12		XP_005262724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UGDH	ENST00000316423.11 linkuse as main transcript	c.1228G>T	p.Ala410Ser	missense_variant	10/12	1	NM_003359.4	ENSP00000319501.6	O60701-1
UGDH	ENST00000506179.5 linkuse as main transcript	c.1228G>T	p.Ala410Ser	missense_variant	10/12	5		ENSP00000421757.1	O60701-1
UGDH	ENST00000501493.6 linkuse as main transcript	c.1027G>T	p.Ala343Ser	missense_variant	9/11	2		ENSP00000422909.1	O60701-2
UGDH	ENST00000507089.5 linkuse as main transcript	c.937G>T	p.Ala313Ser	missense_variant	9/11	2		ENSP00000426560.1	O60701-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251370

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727224

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.85

D;.;D;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Uncertain

0.62

MutationAssessor

Pathogenic

3.9

H;.;H;.

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.72

MutPred

0.68

Loss of catalytic residue at A410 (P = 0.0098);.;Loss of catalytic residue at A410 (P = 0.0098);.;

MVP

0.90

MPC

0.88

ClinPred

0.99

GERP RS

4.8

Varity_R

0.80

gMVP

0.86

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