4-39509779-C-T

Position:

• chr4-39509779-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_003359.4(UGDH):​c.792G>A​(p.Lys264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,603,872 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000078 (2 hom.)
• Consequence: UGDH NM_003359.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 4-39509779-C-T is Benign according to our data. Variant chr4-39509779-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1285104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000335 (51/152342) while in subpopulation AFR AF= 0.00115 (48/41580). AF 95% confidence interval is 0.000894. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGDH	NM_003359.4	c.792G>A	p.Lys264=	synonymous_variant	6/12	ENST00000316423.11
UGDH	NM_001184700.2	c.591G>A	p.Lys197=	synonymous_variant	5/11
UGDH	NM_001184701.2	c.501G>A	p.Lys167=	synonymous_variant	5/11
UGDH	XM_005262667.4	c.831G>A	p.Lys277=	synonymous_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGDH	ENST00000316423.11	c.792G>A	p.Lys264=	synonymous_variant	6/12	1	NM_003359.4	P1
UGDH	ENST00000506179.5	c.792G>A	p.Lys264=	synonymous_variant	6/12	5		P1
UGDH	ENST00000501493.6	c.591G>A	p.Lys197=	synonymous_variant	5/11	2
UGDH	ENST00000507089.5	c.501G>A	p.Lys167=	synonymous_variant	5/11	2

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000104 AC: 25 AN: 240740 Hom.: 0 AF XY: 0.000100 AC XY: 13 AN XY: 130024

Gnomad AFR exome AF: 0.000994

Gnomad AMR exome AF: 0.000157

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: 0.0000271

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.0000778 AC: 113 AN: 1451530 Hom.: 2 Cov.: 30 AF XY: 0.0000942 AC XY: 68 AN XY: 721730

Gnomad4 AFR exome AF: 0.00222

Gnomad4 AMR exome AF: 0.000168

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000541

Gnomad4 OTH exome AF: 0.000350

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.000362 AC XY: 27 AN XY: 74500

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.000131

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

Alfa AF: 0.000254 Hom.: 0

Bravo AF: 0.000427

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	UGDH: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	8.9
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs116145557; hg19: chr4-39511399;