4-114623557-CA-TC

Variant names:

• chr4-114623557-CA-TC
• NM_001128174.3:c.677_678delCAinsTC
• UGT8 p.Pro226Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001128174.3(UGT8):​c.677_678delCAinsTC​(p.Pro226Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: UGT8 NM_001128174.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.81
• Publications: 0 publications found

Genes affected

UGT8 (HGNC:12555): (UDP glycosyltransferase 8) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. It catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central and peripheral nervous systems. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128174.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT8	NM_001128174.3	MANE Select	c.677_678delCAinsTC	p.Pro226Leu	missense	N/A	NP_001121646.2	Q16880
	UGT8	NM_001322112.2		c.677_678delCAinsTC	p.Pro226Leu	missense	N/A	NP_001309041.2	Q16880
	UGT8	NM_001322113.2		c.677_678delCAinsTC	p.Pro226Leu	missense	N/A	NP_001309042.2	Q16880

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT8	ENST00000310836.11	TSL:1 MANE Select	c.677_678delCAinsTC	p.Pro226Leu	missense	N/A	ENSP00000311648.6	Q16880
	UGT8	ENST00000394511.3	TSL:1	c.677_678delCAinsTC	p.Pro226Leu	missense	N/A	ENSP00000378019.3	Q16880
	UGT8	ENST00000507710.2	TSL:3	c.677_678delCAinsTC	p.Pro226Leu	missense	N/A	ENSP00000421446.2	Q16880

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-115544713;