Genetic Variant UGGT1:p.Ser216Ser (chr2-128113210-A-G) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_020120.4(UGGT1):c.648A>G(p.Ser216Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000824 in 1,612,794 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 30)

Exomes 𝑓: 0.00045 ( 5 hom. )

Consequence

UGGT1
NM_020120.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.101

Publications

3 publications found

Variant links:

Genes affected

UGGT1 (HGNC:15663): (UDP-glucose glycoprotein glucosyltransferase 1) 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]

UGGT1 Gene-Disease associations (from GenCC):

disorder of protein N-glycosylation
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

UGGT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-128113210-A-G is Benign according to our data. Variant chr2-128113210-A-G is described in ClinVar as [Benign]. Clinvar id is 778001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.101 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGGT1	NM_020120.4 link	c.648A>G	p.Ser216Ser	synonymous_variant	Exon 6 of 41	ENST00000259253.11	NP_064505.1	Q9NYU2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11 link	c.648A>G	p.Ser216Ser	synonymous_variant	Exon 6 of 41	1	NM_020120.4	ENSP00000259253.6		Q9NYU2-1

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

669

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00107

AC:

268

AN:

249738

AF XY:

0.000733

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.000646

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000449

AC:

656

AN:

1460428

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

277

AN XY:

726558

show subpopulations

African (AFR)

AF:

0.0143

AC:

479

AN:

33426

American (AMR)

AF:

0.000742

AC:

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00278

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

1111360

Other (OTH)

AF:

0.00134

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00442

AC:

673

AN:

152366

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

305

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0154

AC:

639

AN:

41586

American (AMR)

AF:

0.00150

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.00476

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.1

(source)

DANN

Benign

0.60

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism

(source)

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

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2-128113210-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over