NM_020121.4:c.4105G>A

Variant names:

• chr13-95854379-C-T
• rs145358686
• NM_020121.4:c.4105G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP4_Strong BP6_Very_Strong BS2

The NM_020121.4(UGGT2):​c.4105G>A​(p.Gly1369Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,808 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (27 hom.)
• Consequence: UGGT2 NM_020121.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.57
• Publications: 8 publications found

Genes affected

UGGT2 (HGNC:15664): (UDP-glucose glycoprotein glucosyltransferase 2) UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER.[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 10: BayesDel_noAF, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when AlphaMissense, BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.059627384).
• BP6: Variant 13-95854379-C-T is Benign according to our data. Variant chr13-95854379-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 774710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020121.4. 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
	UGGT2	NM_020121.4	MANE Select	c.4105G>A	p.Gly1369Arg	missense	Exon 35 of 39	NP_064506.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGGT2	ENST00000376747.8	TSL:1 MANE Select	c.4105G>A	p.Gly1369Arg	missense	Exon 35 of 39	ENSP00000365938.3	Q9NYU1-1
	UGGT2	ENST00000943424.1		c.4186G>A	p.Gly1396Arg	missense	Exon 36 of 40	ENSP00000613483.1
	UGGT2	ENST00000943423.1		c.4138G>A	p.Gly1380Arg	missense	Exon 36 of 40	ENSP00000613482.1

Frequencies

GnomAD3 genomes AF: 0.00373 AC: 567 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00326 AC: 819 AN: 251134 AF XY: 0.00326

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00656

Gnomad NFE exome AF: 0.00479

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00512 AC: 7480 AN: 1461532 Hom.: 27 Cov.: 30 AF XY: 0.00493 AC XY: 3584 AN XY: 727070

African (AFR) AF: 0.000837 AC: 28 AN: 33464

American (AMR) AF: 0.00145 AC: 65 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00164 AC: 141 AN: 86228

European-Finnish (FIN) AF: 0.00595 AC: 318 AN: 53406

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5762

European-Non Finnish (NFE) AF: 0.00597 AC: 6636 AN: 1111822

Other (OTH) AF: 0.00455 AC: 275 AN: 60378

GnomAD4 genome AF: 0.00372 AC: 567 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.00357 AC XY: 266 AN XY: 74452

African (AFR) AF: 0.00103 AC: 43 AN: 41562

American (AMR) AF: 0.00268 AC: 41 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00588 AC: 400 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00437 Hom.: 2

Bravo AF: 0.00309

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00301 AC: 366

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00498

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.060	T
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		7.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.56		Gain of catalytic residue at K1374 (P = 0.0055)
MVP		0.69
MPC		0.39
ClinPred		0.14	T
GERP RS		5.4
Varity_R		0.91
gMVP		0.84
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs145358686; hg19: chr13-96506633;