dbSNP rs761985145: UGT3A1:p.Met398Ile (chr5-35955746-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152404.4(UGT3A1):c.1194G>C(p.Met398Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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 the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M398V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

UGT3A1
NM_152404.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.389

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049919724).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152404.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT3A1	NM_152404.4	MANE Select	c.1194G>C	p.Met398Ile	missense	Exon 6 of 7	NP_689617.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGT3A1	ENST00000274278.8	TSL:1 MANE Select	c.1194G>C	p.Met398Ile	missense	Exon 6 of 7	ENSP00000274278.3	Q6NUS8-1
UGT3A1	ENST00000876682.1		c.1092G>C	p.Met364Ile	missense	Exon 5 of 6	ENSP00000546741.1
UGT3A1	ENST00000503189.5	TSL:2	c.1194G>C	p.Met398Ile	missense	Exon 6 of 6	ENSP00000427079.1	B7Z8Q8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251486

AF XY:

0.0000515

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000209

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.3

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.78

M_CAP

Benign

0.0027

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.39

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.55

REVEL

Benign

0.084

Sift

Benign

1.0

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.14

MutPred

0.68

Loss of disorder (P = 0.0921)

MVP

0.067

MPC

0.028

ClinPred

0.016

GERP RS

-0.99

Varity_R

0.12

gMVP

0.22

Mutation Taster

=94/6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over