rs553189244

Variant names:

• chr4-68929997-C-A
• rs553189244
• NM_024743.4:c.1400G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-68929997-C-A
• chr4-68929997-C-G
• chr4-68929997-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024743.4(UGT2A3):​c.1400G>T​(p.Arg467Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R467H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UGT2A3 NM_024743.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

Genes affected

UGT2A3 (HGNC:28528): (UDP glucuronosyltransferase family 2 member A3) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024743.4. 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
	UGT2A3	NM_024743.4	MANE Select	c.1400G>T	p.Arg467Leu	missense	Exon 6 of 6	NP_079019.3
	UGT2A3	NR_024010.2		n.1541G>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A3	ENST00000251566.9	TSL:1 MANE Select	c.1400G>T	p.Arg467Leu	missense	Exon 6 of 6	ENSP00000251566.4	Q6UWM9
	UGT2A3	ENST00000852414.1		c.1418G>T	p.Arg473Leu	missense	Exon 6 of 6	ENSP00000522473.1
	UGT2A3	ENST00000852415.1		c.1268G>T	p.Arg423Leu	missense	Exon 5 of 5	ENSP00000522474.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461444 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727042

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111678

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	4.2	H
PhyloP100		1.8
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.94	P
Vest4		0.52
MutPred		0.77		Gain of catalytic residue at R467 (P = 0.0138)
MVP		0.70
MPC		0.020
ClinPred		1.0	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.44
Mutation Taster		=40/60	disease causing

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

Other links and lift over

dbSNP: rs553189244; hg19: chr4-69795715;