9-111914647-T-TA

Position:

• chr9-111914647-T-TA

Variant summary

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

The NM_003358.3(UGCG):​c.142dupA​(p.Ser48fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGCG NM_003358.3 frameshift
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 U:1
• Conservation: PhyloP100: 4.88

Genes affected

UGCG (HGNC:12524): (UDP-glucose ceramide glucosyltransferase) This gene encodes an enzyme that catalyzes the first glycosylation step in the biosynthesis of glycosphingolipids, which are membrane components containing lipid and sugar moieties. The product of this reaction is glucosylceramide, which is the core structure of many glycosphingolipids. [provided by RefSeq, Dec 2014]

UGCG (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGCG	NM_003358.3	c.142dupA	p.Ser48fs	frameshift_variant	2/9	ENST00000374279.4	NP_003349.1
UGCG	XM_017015107.2	c.142dupA	p.Ser48fs	frameshift_variant	2/6		XP_016870596.1
UGCG	XM_047423844.1	c.-322_-321insA		upstream_gene_variant			XP_047279800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGCG	ENST00000374279.4	c.142dupA	p.Ser48fs	frameshift_variant	2/9	1	NM_003358.3	ENSP00000363397.3
UGCG	ENST00000489355.1	n.181dupA		non_coding_transcript_exon_variant	2/2	2
UGCG	ENST00000490110.5	n.157dupA		non_coding_transcript_exon_variant	2/6	3
UGCG	ENST00000495085.1	n.157dupA		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital nonbullous ichthyosiform erythroderma Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Apr 29, 2021

- -

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Feb 09, 2023

- -

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114676927;