Variant rs4148254 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128174.3(UGT8):c.677C>T(p.Pro226Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,613,928 control chromosomes in the GnomAD database, including 1,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.031 ( 133 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1429 hom. )

Consequence

UGT8
NM_001128174.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.81

Variant links:

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]

UGT8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025598109).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT8	NM_001128174.3 linkuse as main transcript	c.677C>T	p.Pro226Leu	missense_variant	2/6	ENST00000310836.11	NP_001121646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT8	ENST00000310836.11 linkuse as main transcript	c.677C>T	p.Pro226Leu	missense_variant	2/6	1	NM_001128174.3	ENSP00000311648	P1
UGT8	ENST00000394511.3 linkuse as main transcript	c.677C>T	p.Pro226Leu	missense_variant	1/5	1		ENSP00000378019	P1

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4690

AN:

151970

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00674

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0528

Gnomad ASJ

AF:

0.0724

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0565

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0473

AC:

11895

AN:

251426

Hom.:

501

AF XY:

0.0461

AC XY:

6265

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00480

Gnomad AMR exome

AF:

0.0850

Gnomad ASJ exome

AF:

0.0660

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0318

Gnomad OTH exome

AF:

0.0384

GnomAD4 exome

AF:

0.0348

AC:

50852

AN:

1461840

Hom.:

1429

Cov.:

AF XY:

0.0354

AC XY:

25750

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.0807

Gnomad4 ASJ exome

AF:

0.0676

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.0497

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0309

AC:

4692

AN:

152088

Hom.:

133

Cov.:

AF XY:

0.0309

AC XY:

2297

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00672

Gnomad4 AMR

AF:

0.0530

Gnomad4 ASJ

AF:

0.0724

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.0568

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0317

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0372

Hom.:

276

Bravo

AF:

0.0346

TwinsUK

AF:

0.0313

AC:

116

ALSPAC

AF:

0.0353

AC:

136

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.0317

AC:

273

ExAC

AF:

0.0447

AC:

5424

Asia WGS

AF:

0.100

AC:

348

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;D

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.7e-10

P;P

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.39

B;B

Vest4

0.56

MPC

0.98

ClinPred

0.046

GERP RS

5.5

Varity_R

0.25

gMVP

0.83

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over