5-36049019-G-A

Position:

• chr5-36049019-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174914.4(UGT3A2):​c.713C>T​(p.Ser238Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: UGT3A2 NM_174914.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153

Genes affected

UGT3A2 (HGNC:27266): (UDP glycosyltransferase family 3 member A2) Enables UDP-glycosyltransferase activity. Acts upstream of or within cellular response to genistein. 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10027394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT3A2	NM_174914.4	c.713C>T	p.Ser238Phe	missense_variant	4/7	ENST00000282507.8	NP_777574.2
UGT3A2	NM_001168316.2	c.611C>T	p.Ser204Phe	missense_variant	3/6		NP_001161788.1
UGT3A2	XM_011513988.2	c.794C>T	p.Ser265Phe	missense_variant	5/8		XP_011512290.1
UGT3A2	NR_031764.2	n.404+2851C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT3A2	ENST00000282507.8	c.713C>T	p.Ser238Phe	missense_variant	4/7	1	NM_174914.4	ENSP00000282507	P1
UGT3A2	ENST00000513300.5	c.611C>T	p.Ser204Phe	missense_variant	3/6	2		ENSP00000427404
UGT3A2	ENST00000504685.5	c.311+2851C>T		intron_variant, NMD_transcript_variant		2		ENSP00000426017
UGT3A2	ENST00000504954.1	n.494+2851C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.713C>T (p.S238F) alteration is located in exon 4 (coding exon 4) of the UGT3A2 gene. This alteration results from a C to T substitution at nucleotide position 713, causing the serine (S) at amino acid position 238 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.29
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.069
Sift	Benign	0.032	D;T
Sift4G	Benign	0.34	T;T
Polyphen		0.53	P;.
Vest4		0.15
MutPred		0.60		Loss of disorder (P = 0.0304);.;
MVP		0.45
MPC		0.067
ClinPred		0.096	T
GERP RS		2.6
Varity_R		0.055
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs1200210224; hg19: chr5-36049121;