chr4-39500207-G-A

Position:

• chr4-39500207-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003359.4(UGDH):​c.1421C>T​(p.Ala474Val) variant causes a missense change involving the alteration of a 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGDH NM_003359.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.51

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15231931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGDH	NM_003359.4	c.1421C>T	p.Ala474Val	missense_variant	12/12	ENST00000316423.11
UGDH	NM_001184700.2	c.1220C>T	p.Ala407Val	missense_variant	11/11
UGDH	NM_001184701.2	c.1130C>T	p.Ala377Val	missense_variant	11/11
UGDH	XM_005262667.4	c.1460C>T	p.Ala487Val	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGDH	ENST00000316423.11	c.1421C>T	p.Ala474Val	missense_variant	12/12	1	NM_003359.4	P1
UGDH	ENST00000506179.5	c.1421C>T	p.Ala474Val	missense_variant	12/12	5		P1
UGDH	ENST00000501493.6	c.1220C>T	p.Ala407Val	missense_variant	11/11	2
UGDH	ENST00000507089.5	c.1130C>T	p.Ala377Val	missense_variant	11/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.1421C>T (p.A474V) alteration is located in exon 12 (coding exon 11) of the UGDH gene. This alteration results from a C to T substitution at nucleotide position 1421, causing the alanine (A) at amino acid position 474 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;T;.
Eigen	Benign	-0.052
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.69	N;.;N;.
MutationTaster	Benign	0.97	N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.012	B;.;B;.
Vest4		0.30
MutPred		0.14		Loss of disorder (P = 0.217);.;Loss of disorder (P = 0.217);.;
MVP		0.86
MPC		0.27
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.10
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-39501827;