13-95854379-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3 BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 7.57

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

Verdict is Benign. Variant got -9 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 9: BayesDel_noAF, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN, 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 id is 774710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGGT2	NM_020121.4	c.4105G>A	p.Gly1369Arg	missense_variant	35/39	ENST00000376747.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGGT2	ENST00000376747.8	c.4105G>A	p.Gly1369Arg	missense_variant	35/39	1	NM_020121.4	P1

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

GnomAD3 exomes AF: 0.00326 AC: 819 AN: 251134 Hom.: 2 AF XY: 0.00326 AC XY: 443 AN XY: 135720

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 SAS exome AF: 0.00160

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

Gnomad4 AFR exome AF: 0.000837

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00164

Gnomad4 FIN exome AF: 0.00595

Gnomad4 NFE exome AF: 0.00597

Gnomad4 OTH exome AF: 0.00455

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

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00556

Gnomad4 NFE AF: 0.00588

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00491 Hom.: 0

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	D
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

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: rs145358686; hg19: chr13-96506633;