2-128109655-C-G

Position:

• chr2-128109655-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020120.4(UGGT1):​c.430C>G​(p.Pro144Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGGT1 NM_020120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29548728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGGT1	NM_020120.4	c.430C>G	p.Pro144Ala	missense_variant	5/41	ENST00000259253.11	NP_064505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11	c.430C>G	p.Pro144Ala	missense_variant	5/41	1	NM_020120.4	ENSP00000259253	P1
UGGT1	ENST00000376723.7	c.*470C>G		3_prime_UTR_variant, NMD_transcript_variant	5/41	1		ENSP00000365913
UGGT1	ENST00000438277.5	c.*18C>G		3_prime_UTR_variant, NMD_transcript_variant	3/26	1		ENSP00000392701

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.430C>G (p.P144A) alteration is located in exon 5 (coding exon 5) of the UGGT1 gene. This alteration results from a C to G substitution at nucleotide position 430, causing the proline (P) at amino acid position 144 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.13
Sift	Benign	0.070	T
Sift4G	Benign	0.14	T
Polyphen		0.73	P
Vest4		0.43
MutPred		0.30		Loss of glycosylation at P144 (P = 0.0258);
MVP		0.46
MPC		0.087
ClinPred		0.94	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-128867229;