9-111914651-A-G

Variant names:

• chr9-111914651-A-G
• rs1838079254
• NM_003358.3:c.145A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003358.3(UGCG):​c.145A>G​(p.Lys49Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: UGCG NM_003358.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ichthyosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13268322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003358.3. 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
	UGCG	NM_003358.3	MANE Select	c.145A>G	p.Lys49Glu	missense	Exon 2 of 9	NP_003349.1	Q16739

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGCG	ENST00000374279.4	TSL:1 MANE Select	c.145A>G	p.Lys49Glu	missense	Exon 2 of 9	ENSP00000363397.3	Q16739
	UGCG	ENST00000915623.1		c.91A>G	p.Lys31Glu	missense	Exon 2 of 9	ENSP00000585682.1
	UGCG	ENST00000856546.1		c.145A>G	p.Lys49Glu	missense	Exon 2 of 9	ENSP00000526605.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461800 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.95	L
PhyloP100		6.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.18
Sift	Benign	0.55	T
Sift4G	Benign	0.98	T
Polyphen		0.0020	B
Vest4		0.35
MutPred		0.41		Loss of methylation at K49 (P = 0.0026)
MVP		0.37
MPC		1.0
ClinPred		0.75	D
GERP RS		5.7
Varity_R		0.33
gMVP		0.61
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs1838079254; hg19: chr9-114676931;