chr5-36035968-C-A

Position:

• chr5-36035968-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_174914.4(UGT3A2):​c.1302G>T​(p.Lys434Asn) 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. 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: -0.158

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38811338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT3A2	NM_174914.4	c.1302G>T	p.Lys434Asn	missense_variant	7/7	ENST00000282507.8	NP_777574.2
UGT3A2	NM_001168316.2	c.1200G>T	p.Lys400Asn	missense_variant	6/6		NP_001161788.1
UGT3A2	XM_011513988.2	c.1383G>T	p.Lys461Asn	missense_variant	8/8		XP_011512290.1
UGT3A2	NR_031764.2	n.863G>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT3A2	ENST00000282507.8	c.1302G>T	p.Lys434Asn	missense_variant	7/7	1	NM_174914.4	ENSP00000282507	P1
UGT3A2	ENST00000513300.5	c.1200G>T	p.Lys400Asn	missense_variant	6/6	2		ENSP00000427404
UGT3A2	ENST00000504685.5	c.*407G>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000426017

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

Oct 12, 2022

The c.1302G>T (p.K434N) alteration is located in exon 7 (coding exon 7) of the UGT3A2 gene. This alteration results from a G to T substitution at nucleotide position 1302, causing the lysine (K) at amino acid position 434 to be replaced by an asparagine (N). 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.00091	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.7	H;.
MutationTaster	Benign	0.61	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.21
MutPred		0.77		Loss of ubiquitination at K434 (P = 0.0199);.;
MVP		0.14
MPC		0.30
ClinPred		1.0	D
GERP RS		-2.4
Varity_R		0.67
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-36036070;