rs956955757

Variant names:

• chr13-95860797-C-A
• rs956955757
• NM_020121.4:c.3731G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-95860797-C-A
• chr13-95860797-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020121.4(UGGT2):​c.3731G>T​(p.Arg1244Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000514 in 1,363,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1244H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: UGGT2 NM_020121.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17
• Publications: 2 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

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.3731G>T	p.Arg1244Leu	missense	Exon 32 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.3731G>T	p.Arg1244Leu	missense	Exon 32 of 39	ENSP00000365938.3	Q9NYU1-1
	UGGT2	ENST00000943424.1		c.3812G>T	p.Arg1271Leu	missense	Exon 33 of 40	ENSP00000613483.1
	UGGT2	ENST00000943423.1		c.3764G>T	p.Arg1255Leu	missense	Exon 33 of 40	ENSP00000613482.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000514 AC: 7 AN: 1363192 Hom.: 0 Cov.: 28 AF XY: 0.00000592 AC XY: 4 AN XY: 675896

African (AFR) AF: 0.00 AC: 0 AN: 29284

American (AMR) AF: 0.00 AC: 0 AN: 32772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23228

East Asian (EAS) AF: 0.00 AC: 0 AN: 36376

South Asian (SAS) AF: 0.00 AC: 0 AN: 66728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 0.00000658 AC: 7 AN: 1063452

Other (OTH) AF: 0.00 AC: 0 AN: 55488

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.024	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		5.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.68		Gain of catalytic residue at G1239 (P = 0.0182)
MVP		0.72
MPC		0.39
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.75
gMVP		0.81
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs956955757; hg19: chr13-96513051; COSMIC: COSV65078624; COSMIC: COSV65078624;