chr4-39505377-G-GA

Position:

• chr4-39505377-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003359.4(UGDH):​c.1038-8_1038-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 1,432,578 control chromosomes in the GnomAD database, including 16 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (1 hom., cov: 25)
  • Exomes 𝑓: 0.0072 (15 hom.)
• Consequence: UGDH NM_003359.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.793

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 -10 ACMG points.

• BP6: Variant 4-39505377-G-GA is Benign according to our data. Variant chr4-39505377-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1711589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00505 (752/149008) while in subpopulation NFE AF= 0.00745 (499/67014). AF 95% confidence interval is 0.00691. There are 1 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGDH	NM_003359.4	c.1038-8_1038-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000316423.11
UGDH	NM_001184700.2	c.837-8_837-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
UGDH	NM_001184701.2	c.747-8_747-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
UGDH	XM_005262667.4	c.1077-8_1077-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGDH	ENST00000316423.11	c.1038-8_1038-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003359.4	P1
UGDH	ENST00000501493.6	c.837-8_837-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
UGDH	ENST00000506179.5	c.1038-8_1038-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		P1
UGDH	ENST00000507089.5	c.747-8_747-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 751 AN: 148906 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.00115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00619

Gnomad ASJ AF: 0.00612

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00741

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00745

Gnomad OTH AF: 0.00733

GnomAD4 exome AF: 0.00724 AC: 9289 AN: 1283570 Hom.: 15 Cov.: 24 AF XY: 0.00727 AC XY: 4600 AN XY: 632796

Gnomad4 AFR exome AF: 0.00151

Gnomad4 AMR exome AF: 0.00620

Gnomad4 ASJ exome AF: 0.00766

Gnomad4 EAS exome AF: 0.000688

Gnomad4 SAS exome AF: 0.00389

Gnomad4 FIN exome AF: 0.00958

Gnomad4 NFE exome AF: 0.00774

Gnomad4 OTH exome AF: 0.00747

GnomAD4 genome AF: 0.00505 AC: 752 AN: 149008 Hom.: 1 Cov.: 25 AF XY: 0.00519 AC XY: 376 AN XY: 72474

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00618

Gnomad4 ASJ AF: 0.00612

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00106

Gnomad4 FIN AF: 0.00741

Gnomad4 NFE AF: 0.00745

Gnomad4 OTH AF: 0.00725

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

UGDH: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs33942301; hg19: chr4-39506997;