2-128107929-C-T

Variant names:

• chr2-128107929-C-T
• rs73957674
• NM_020120.4:c.278-9C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_020120.4(UGGT1):​c.278-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,613,646 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (7 hom.)
• Consequence: UGGT1 NM_020120.4 intron
• Scores: Splicing: ADA: 0.00001959
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.964
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-128107929-C-T is Benign according to our data. Variant chr2-128107929-C-T is described in ClinVar as [Benign]. Clinvar id is 713049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGGT1	NM_020120.4	c.278-9C>T		intron_variant	Intron 3 of 40	ENST00000259253.11	NP_064505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11	c.278-9C>T		intron_variant	Intron 3 of 40	1	NM_020120.4	ENSP00000259253.6
UGGT1	ENST00000376723.7	n.*318-9C>T		intron_variant	Intron 3 of 40	1		ENSP00000365913.3
UGGT1	ENST00000438277.5	n.162-1705C>T		intron_variant	Intron 2 of 25	1		ENSP00000392701.1
UGGT1	ENST00000430075.5	n.*135-9C>T		intron_variant	Intron 4 of 4	4		ENSP00000400426.1

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 374 AN: 152130 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000764 AC: 192 AN: 251192 AF XY: 0.000670

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000465 AC: 680 AN: 1461398 Hom.: 7 Cov.: 30 AF XY: 0.000464 AC XY: 337 AN XY: 726982

African (AFR) AF: 0.00830 AC: 278 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000696 AC: 60 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.0127 AC: 73 AN: 5768

European-Non Finnish (NFE) AF: 0.000151 AC: 168 AN: 1111630

Other (OTH) AF: 0.000828 AC: 50 AN: 60378

GnomAD4 genome AF: 0.00246 AC: 374 AN: 152248 Hom.: 1 Cov.: 33 AF XY: 0.00246 AC XY: 183 AN XY: 74438

African (AFR) AF: 0.00778 AC: 323 AN: 41540

American (AMR) AF: 0.00144 AC: 22 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68004

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00146 Hom.: 1

Bravo AF: 0.00273

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.6
DANN	Benign	0.79
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.088
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: rs73957674; hg19: chr2-128865503;