NM_152404.4:c.1549G>C

Variant names:

• chr5-35954225-C-G
• rs1739264211
• NM_152404.4:c.1549G>C

Variant summary

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

The NM_152404.4(UGT3A1):​c.1549G>C​(p.Ala517Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,824 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000068 (1 hom.)
• Consequence: UGT3A1 NM_152404.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.174

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

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=0.14254934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT3A1	NM_152404.4	c.1549G>C	p.Ala517Pro	missense_variant	Exon 7 of 7	ENST00000274278.8	NP_689617.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT3A1	ENST00000274278.8	c.1549G>C	p.Ala517Pro	missense_variant	Exon 7 of 7	1	NM_152404.4	ENSP00000274278.3
UGT3A1	ENST00000515801.5	n.*3346G>C		non_coding_transcript_exon_variant	Exon 8 of 8	2		ENSP00000427630.1
UGT3A1	ENST00000515801.5	n.*3346G>C		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000427630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461824 Hom.: 1 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727210

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1549G>C (p.A517P) alteration is located in exon 7 (coding exon 7) of the UGT3A1 gene. This alteration results from a G to C substitution at nucleotide position 1549, causing the alanine (A) at amino acid position 517 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.035	D
Sift4G	Uncertain	0.047	D
Polyphen		0.95	P
Vest4		0.13
MutPred		0.48		Gain of glycosylation at A517 (P = 0.048);
MVP		0.14
MPC		0.032
ClinPred		0.48	T
GERP RS		-2.4
Varity_R		0.19
gMVP		0.070

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: rs1739264211; hg19: chr5-35954327;