UGT3A1 p.Met424Ile

Variant names:

• chr5-35955668-C-A
• NM_152404.4:c.1272G>T
• UGT3A1 p.Met424Ile

Your query was ambiguous. Multiple possible variants found:

• chr5-35955668-C-A
• chr5-35955668-C-G
• chr5-35955668-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152404.4(UGT3A1):​c.1272G>T​(p.Met424Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UGT3A1 NM_152404.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.817
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22487342).

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.1272G>T	p.Met424Ile	missense	Exon 6 of 7	NP_689617.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT3A1	ENST00000274278.8	TSL:1 MANE Select	c.1272G>T	p.Met424Ile	missense	Exon 6 of 7	ENSP00000274278.3	Q6NUS8-1
	UGT3A1	ENST00000876682.1		c.1170G>T	p.Met390Ile	missense	Exon 5 of 6	ENSP00000546741.1
	UGT3A1	ENST00000503189.5	TSL:2	c.1272G>T	p.Met424Ile	missense	Exon 6 of 6	ENSP00000427079.1	B7Z8Q8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.82
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.071
Sift	Benign	0.19	T
Sift4G	Benign	0.44	T
Varity_R		0.24
gMVP		0.14
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-35955770;

COSMIC: COSV57095974;

COSMIC: COSV57095974;