5-35965868-A-C

Variant names:

• chr5-35965868-A-C
• rs3756669
• NM_152404.4:c.361T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000274278.8(UGT3A1):​c.361T>G​(p.Cys121Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,599,150 control chromosomes in the GnomAD database, including 23,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C121Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1890 hom., cov: 33)
  • Exomes 𝑓: 0.16 (21112 hom.)
• Consequence: UGT3A1 ENST00000274278.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000274278.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT3A1	NM_152404.4	MANE Select	c.361T>G	p.Cys121Gly	missense	Exon 4 of 7	NP_689617.3
	UGT3A1	NM_001171873.2		c.199T>G	p.Cys67Gly	missense	Exon 5 of 6	NP_001165344.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT3A1	ENST00000274278.8	TSL:1 MANE Select	c.361T>G	p.Cys121Gly	missense	Exon 4 of 7	ENSP00000274278.3
	UGT3A1	ENST00000625798.2	TSL:1	c.199T>G	p.Cys67Gly	missense	Exon 5 of 6	ENSP00000487376.1
	UGT3A1	ENST00000503189.5	TSL:2	c.361T>G	p.Cys121Gly	missense	Exon 4 of 6	ENSP00000427079.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19971 AN: 152142 Hom.: 1887 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.138

GnomAD2 exomes AF: 0.191 AC: 45214 AN: 236240 AF XY: 0.197

Gnomad AFR exome AF: 0.0347

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.406

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.159 AC: 229392 AN: 1446890 Hom.: 21112 Cov.: 32 AF XY: 0.164 AC XY: 117462 AN XY: 718410

African (AFR) AF: 0.0339 AC: 1110 AN: 32790

American (AMR) AF: 0.233 AC: 9869 AN: 42366

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3633 AN: 25538

East Asian (EAS) AF: 0.332 AC: 13144 AN: 39570

South Asian (SAS) AF: 0.333 AC: 27566 AN: 82730

European-Finnish (FIN) AF: 0.127 AC: 6708 AN: 52746

Middle Eastern (MID) AF: 0.144 AC: 818 AN: 5686

European-Non Finnish (NFE) AF: 0.141 AC: 156340 AN: 1105672

Other (OTH) AF: 0.171 AC: 10204 AN: 59792

GnomAD4 genome AF: 0.131 AC: 19986 AN: 152260 Hom.: 1890 Cov.: 33 AF XY: 0.135 AC XY: 10080 AN XY: 74446

African (AFR) AF: 0.0369 AC: 1535 AN: 41570

American (AMR) AF: 0.182 AC: 2779 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3464

East Asian (EAS) AF: 0.379 AC: 1967 AN: 5184

South Asian (SAS) AF: 0.343 AC: 1657 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1365 AN: 10610

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9808 AN: 67998

Other (OTH) AF: 0.141 AC: 299 AN: 2116

Alfa AF: 0.147 Hom.: 5957

Bravo AF: 0.127

TwinsUK AF: 0.141 AC: 522

ALSPAC AF: 0.145 AC: 557

ESP6500AA AF: 0.0356 AC: 157

ESP6500EA AF: 0.140 AC: 1201

ExAC AF: 0.187 AC: 22638

Asia WGS AF: 0.322 AC: 1121 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.098	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-9.3	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.38
MPC		0.21
ClinPred		0.11	T
GERP RS		3.0
Varity_R		0.91
gMVP		0.64
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 0

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

Other links and lift over

dbSNP: rs3756669; hg19: chr5-35965970; COSMIC: COSV57097293;