Variant 9-111914651-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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. 14/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13268322).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGCG	NM_003358.3 linkuse as main transcript	c.145A>G	p.Lys49Glu	missense_variant	2/9	ENST00000374279.4
UGCG	XM_017015107.2 linkuse as main transcript	c.145A>G	p.Lys49Glu	missense_variant	2/6
UGCG	XM_047423844.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
UGCG	ENST00000374279.4 linkuse as main transcript	c.145A>G	p.Lys49Glu	missense_variant	2/9	1	NM_003358.3	P1
UGCG	ENST00000489355.1 linkuse as main transcript	n.184A>G		non_coding_transcript_exon_variant	2/2	2
UGCG	ENST00000490110.5 linkuse as main transcript	n.160A>G		non_coding_transcript_exon_variant	2/6	3
UGCG	ENST00000495085.1 linkuse as main transcript	n.160A>G		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.145A>G (p.K49E) alteration is located in exon 2 (coding exon 2) of the UGCG gene. This alteration results from a A to G substitution at nucleotide position 145, causing the lysine (K) at amino acid position 49 to be replaced by a glutamic acid (E). 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

0.085

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.26

Eigen

Benign

-0.22

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.013

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.95

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.020

REVEL

Benign

0.18

Sift

Benign

0.55

Sift4G

Benign

0.98

Polyphen

0.0020

Vest4

0.35

MutPred

0.41

Loss of methylation at K49 (P = 0.0026);

MVP

0.37

MPC

1.0

ClinPred

0.75

GERP RS

5.7

Varity_R

0.33

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over