4-39505325-A-G

Position:

• chr4-39505325-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_003359.4(UGDH):​c.1083T>C​(p.Gly361Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGDH NM_003359.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-39505325-A-G is Benign according to our data. Variant chr4-39505325-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGDH	NM_003359.4	c.1083T>C	p.Gly361Gly	synonymous_variant	9/12	ENST00000316423.11	NP_003350.1
UGDH	NM_001184700.2	c.882T>C	p.Gly294Gly	synonymous_variant	8/11		NP_001171629.1
UGDH	NM_001184701.2	c.792T>C	p.Gly264Gly	synonymous_variant	8/11		NP_001171630.1
UGDH	XM_005262667.4	c.1122T>C	p.Gly374Gly	synonymous_variant	9/12		XP_005262724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGDH	ENST00000316423.11	c.1083T>C	p.Gly361Gly	synonymous_variant	9/12	1	NM_003359.4	ENSP00000319501.6
UGDH	ENST00000506179.5	c.1083T>C	p.Gly361Gly	synonymous_variant	9/12	5		ENSP00000421757.1
UGDH	ENST00000501493.6	c.882T>C	p.Gly294Gly	synonymous_variant	8/11	2		ENSP00000422909.1
UGDH	ENST00000507089.5	c.792T>C	p.Gly264Gly	synonymous_variant	8/11	2		ENSP00000426560.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 01, 2023

UGDH: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.46
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1745983376; hg19: chr4-39506945;