5-35954273-A-G

Variant names:

• chr5-35954273-A-G
• NM_152404.4:c.1501T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152404.4(UGT3A1):​c.1501T>C​(p.Trp501Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,878 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. W501G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UGT3A1 NM_152404.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT3A1	NM_152404.4	c.1501T>C	p.Trp501Arg	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.1501T>C	p.Trp501Arg	missense_variant	Exon 7 of 7	1	NM_152404.4	ENSP00000274278.3
UGT3A1	ENST00000515801.5	n.*3298T>C		non_coding_transcript_exon_variant	Exon 8 of 8	2		ENSP00000427630.1
UGT3A1	ENST00000515801.5	n.*3298T>C		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000427630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.0028	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.45
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.50
MutPred		0.79		Gain of methylation at W501 (P = 0.0162);
MVP		0.42
MPC		0.24
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.85
gMVP		0.27

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: chr5-35954375;