chr5-36049107-T-C

Position:

• chr5-36049107-T-C

Variant summary

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

The NM_174914.4(UGT3A2):​c.625A>G​(p.Ser209Gly) 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. 15/23 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)
• Consequence: UGT3A2 NM_174914.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT3A2	NM_174914.4	c.625A>G	p.Ser209Gly	missense_variant	4/7	ENST00000282507.8	NP_777574.2
UGT3A2	NM_001168316.2	c.523A>G	p.Ser175Gly	missense_variant	3/6		NP_001161788.1
UGT3A2	XM_011513988.2	c.706A>G	p.Ser236Gly	missense_variant	5/8		XP_011512290.1
UGT3A2	NR_031764.2	n.404+2763A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT3A2	ENST00000282507.8	c.625A>G	p.Ser209Gly	missense_variant	4/7	1	NM_174914.4	ENSP00000282507	P1
UGT3A2	ENST00000513300.5	c.523A>G	p.Ser175Gly	missense_variant	3/6	2		ENSP00000427404
UGT3A2	ENST00000504685.5	c.311+2763A>G		intron_variant, NMD_transcript_variant		2		ENSP00000426017
UGT3A2	ENST00000504954.1	n.494+2763A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 01, 2022

The c.625A>G (p.S209G) alteration is located in exon 4 (coding exon 4) of the UGT3A2 gene. This alteration results from a A to G substitution at nucleotide position 625, causing the serine (S) at amino acid position 209 to be replaced by a glycine (G). 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	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.047
Sift	Benign	0.54	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0040	B;.
Vest4		0.12
MutPred		0.54		Loss of sheet (P = 0.0011);.;
MVP		0.048
MPC		0.041
ClinPred		0.047	T
GERP RS		-6.2
Varity_R		0.034
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.47		Position offset: -11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-36049209;