Genetic Variant UGT3A1:p.Cys121Gly (chr5-35965868-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_152404.4(UGT3A1):c.361T>G(p.Cys121Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,599,150 control chromosomes in the GnomAD database, including 23,002 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. C121Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.13 ( 1890 hom., cov: 33)

Exomes 𝑓: 0.16 ( 21112 hom. )

Consequence

UGT3A1
NM_152404.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

Publications

36 publications found

Variant links:

Genes affected

UGT3A1 (HGNC:26625): (UDP glycosyltransferase family 3 member A1) Enables glucuronosyltransferase activity. Part of UDP-N-acetylglucosamine transferase complex. [provided by Alliance of Genome Resources, Apr 2022]

UGT3A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT3A1	NM_152404.4 link	c.361T>G	p.Cys121Gly	missense_variant	Exon 4 of 7	ENST00000274278.8	NP_689617.3	Q6NUS8-1A8K444B7Z3N0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT3A1	ENST00000274278.8 link	c.361T>G	p.Cys121Gly	missense_variant	Exon 4 of 7	1	NM_152404.4	ENSP00000274278.3		Q6NUS8-1

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19971

AN:

152142

Hom.:

1887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.138

GnomAD2 exomes

AF:

0.191

AC:

45214

AN:

236240

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.159

AC:

229392

AN:

1446890

Hom.:

21112

Cov.:

AF XY:

0.164

AC XY:

117462

AN XY:

718410

show subpopulations

African (AFR)

AF:

0.0339

AC:

1110

AN:

32790

American (AMR)

AF:

0.233

AC:

9869

AN:

42366

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3633

AN:

25538

East Asian (EAS)

AF:

0.332

AC:

13144

AN:

39570

South Asian (SAS)

AF:

0.333

AC:

27566

AN:

82730

European-Finnish (FIN)

AF:

0.127

AC:

6708

AN:

52746

Middle Eastern (MID)

AF:

0.144

AC:

818

AN:

5686

European-Non Finnish (NFE)

AF:

0.141

AC:

156340

AN:

1105672

Other (OTH)

AF:

0.171

AC:

10204

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

8388

16776

25164

33552

41940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.131

AC:

19986

AN:

152260

Hom.:

1890

Cov.:

AF XY:

0.135

AC XY:

10080

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0369

AC:

1535

AN:

41570

American (AMR)

AF:

0.182

AC:

2779

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3464

East Asian (EAS)

AF:

0.379

AC:

1967

AN:

5184

South Asian (SAS)

AF:

0.343

AC:

1657

AN:

4826

European-Finnish (FIN)

AF:

0.129

AC:

1365

AN:

10610

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9808

AN:

67998

Other (OTH)

AF:

0.141

AC:

299

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

872

1743

2615

3486

4358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.147

Hom.:

5957

Bravo

AF:

0.127

TwinsUK

AF:

0.141

AC:

522

ALSPAC

AF:

0.145

AC:

557

ESP6500AA

AF:

0.0356

AC:

157

ESP6500EA

AF:

0.140

AC:

1201

ExAC

AF:

0.187

AC:

22638

Asia WGS

AF:

0.322

AC:

1121

AN:

3478

EpiCase

AF:

0.148

EpiControl

AF:

0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.098

T;.;.;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.69

T;T;T;.;T

MetaRNN

Benign

0.0048

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.3

M;.;.;.;.

PhyloP100

1.5

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-9.3

D;D;D;.;D

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.38

MPC

0.21

ClinPred

0.11

GERP RS

3.0

Varity_R

0.91

gMVP

0.64

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-35965868-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over