rs4148301

Variant names:

• chr4-69596324-C-T
• rs4148301
• NM_001105677.2:c.949G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

The NM_001105677.2(UGT2A2):​c.949G>A​(p.Gly317Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,606,364 control chromosomes in the GnomAD database, including 6,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (578 hom., cov: 32)
  • Exomes 𝑓: 0.085 (5627 hom.)
• Consequence: UGT2A2 NM_001105677.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.61
• Publications: 22 publications found

Genes affected

UGT2A2 (HGNC:28183): (UDP glucuronosyltransferase family 2 member A2) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A1 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

UGT2A1 (HGNC:12542): (UDP glucuronosyltransferase family 2 member A1 complex locus) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. Members of this protein family play a role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The encoded enzyme is expressed in the olfactory neuroepithelium, which lines the posterior nasal cavity and is exposed to a wide range of odorants and airborne toxic compounds. Hence, this protein has been suggested to be involved in clearing lipophilic odorant molecules from the sensory epithelium. This gene shares exon structure with the UDP glucuronosyltransferase 2A2 family member, which encodes N-terminally distinct isoforms. Polymorphisms in this gene may be associated with the loss of taste and smell that is reported by some individuals during SARS-CoV-2 infection. [provided by RefSeq, Jan 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.0051986873).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105677.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	NM_001105677.2	MANE Select	c.949G>A	p.Gly317Arg	missense	Exon 3 of 6	NP_001099147.2	P0DTE5-1
	UGT2A1	NM_001252275.3	MANE Select	c.997-1075G>A		intron	N/A	NP_001239204.2	P0DTE4-5
	UGT2A1	NM_001389565.1		c.1552G>A	p.Gly518Arg	missense	Exon 5 of 8	NP_001376494.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2A2	ENST00000604629.6	TSL:1 MANE Select	c.949G>A	p.Gly317Arg	missense	Exon 3 of 6	ENSP00000475028.2	P0DTE5-1
	UGT2A1	ENST00000503640.5	TSL:1	c.922G>A	p.Gly308Arg	missense	Exon 3 of 6	ENSP00000424478.1	P0DTE4-1
	UGT2A1	ENST00000286604.9	TSL:1 MANE Select	c.997-1075G>A		intron	N/A	ENSP00000286604.4	P0DTE4-5

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12439 AN: 151930 Hom.: 578 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0518

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.0798 AC: 19772 AN: 247870 AF XY: 0.0815

Gnomad AFR exome AF: 0.0635

Gnomad AMR exome AF: 0.0497

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0487

Gnomad FIN exome AF: 0.0954

Gnomad NFE exome AF: 0.0901

Gnomad OTH exome AF: 0.0992

GnomAD4 exome AF: 0.0850 AC: 123636 AN: 1454314 Hom.: 5627 Cov.: 31 AF XY: 0.0849 AC XY: 61441 AN XY: 723494

African (AFR) AF: 0.0640 AC: 2122 AN: 33166

American (AMR) AF: 0.0558 AC: 2479 AN: 44404

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3897 AN: 25860

East Asian (EAS) AF: 0.0497 AC: 1954 AN: 39320

South Asian (SAS) AF: 0.0650 AC: 5546 AN: 85340

European-Finnish (FIN) AF: 0.0940 AC: 4986 AN: 53064

Middle Eastern (MID) AF: 0.143 AC: 818 AN: 5724

European-Non Finnish (NFE) AF: 0.0870 AC: 96299 AN: 1107462

Other (OTH) AF: 0.0923 AC: 5535 AN: 59974

GnomAD4 genome AF: 0.0818 AC: 12441 AN: 152050 Hom.: 578 Cov.: 32 AF XY: 0.0823 AC XY: 6113 AN XY: 74314

African (AFR) AF: 0.0633 AC: 2624 AN: 41482

American (AMR) AF: 0.0794 AC: 1213 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3466

East Asian (EAS) AF: 0.0515 AC: 266 AN: 5166

South Asian (SAS) AF: 0.0633 AC: 305 AN: 4820

European-Finnish (FIN) AF: 0.102 AC: 1079 AN: 10552

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0902 AC: 6135 AN: 67978

Other (OTH) AF: 0.111 AC: 233 AN: 2106

Alfa AF: 0.0885 Hom.: 2652

Bravo AF: 0.0808

TwinsUK AF: 0.0860 AC: 319

ALSPAC AF: 0.0848 AC: 327

ESP6500AA AF: 0.0763 AC: 336

ESP6500EA AF: 0.0998 AC: 858

ExAC AF: 0.0816 AC: 9903

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	29
DANN	Pathogenic	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.39	T
PhyloP100		7.6
PROVEAN	Pathogenic	-7.4	D
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.96
MutPred		0.35		Gain of MoRF binding (P = 0.0088)
MPC		0.068
ClinPred		0.12	T
GERP RS		5.4
gMVP		0.76
Mutation Taster		=76/24	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4148301; hg19: chr4-70462042; COSMIC: COSV54138928;