Variant 9-111914619-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003358.3(UGCG):c.113A>G(p.Asn38Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.000017 ( 0 hom. )

Consequence

UGCG
NM_003358.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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:

UGCG (HGNC:):

UGCG links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.276694).

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGCG	NM_003358.3 linkuse as main transcript	c.113A>G	p.Asn38Ser	missense_variant	2/9	ENST00000374279.4	NP_003349.1	Q16739A0A024R157
UGCG	XM_017015107.2 linkuse as main transcript	c.113A>G	p.Asn38Ser	missense_variant	2/6		XP_016870596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UGCG	ENST00000374279.4 linkuse as main transcript	c.113A>G	p.Asn38Ser	missense_variant	2/9	1	NM_003358.3	ENSP00000363397.3	Q16739
UGCG	ENST00000489355.1 linkuse as main transcript	n.152A>G		non_coding_transcript_exon_variant	2/2	2
UGCG	ENST00000490110.5 linkuse as main transcript	n.128A>G		non_coding_transcript_exon_variant	2/6	3
UGCG	ENST00000495085.1 linkuse as main transcript	n.128A>G		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251260

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461598

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727096

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Oct 13, 2023

The c.113A>G (p.N38S) 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 113, causing the asparagine (N) at amino acid position 38 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Benign

0.050

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0043

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

REVEL

Benign

0.15

Sift

Uncertain

0.011

Sift4G

Uncertain

0.030

Polyphen

0.075

Vest4

0.23

MVP

0.47

MPC

0.61

ClinPred

0.59

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.49

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