dbSNP rs759111551: UGT8:p.Ile368Leu (chr4-114668144-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128174.3(UGT8):c.1102A>C(p.Ile368Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I368V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UGT8
NM_001128174.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.56

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.401455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT8	NM_001128174.3 link	c.1102A>C	p.Ile368Leu	missense_variant	Exon 5 of 6	ENST00000310836.11	NP_001121646.2	Q16880

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UGT8	ENST00000310836.11 link	c.1102A>C	p.Ile368Leu	missense_variant	Exon 5 of 6	1	NM_001128174.3	ENSP00000311648.6	Q16880
UGT8	ENST00000394511.3 link	c.1102A>C	p.Ile368Leu	missense_variant	Exon 4 of 5	1		ENSP00000378019.3	Q16880
UGT8	ENST00000507710.2 link	c.1102A>C	p.Ile368Leu	missense_variant	Exon 6 of 7	3		ENSP00000421446.2	D6RFW2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111774

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.093

Eigen_PC

Benign

0.086

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.1

L;L

PhyloP100

7.6

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.085

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0010

B;B

Vest4

0.28

MutPred

0.71

Gain of glycosylation at Y369 (P = 0.027);Gain of glycosylation at Y369 (P = 0.027);

MVP

0.68

MPC

0.29

ClinPred

0.80

GERP RS

5.5

Varity_R

0.34

gMVP

0.82

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over