chr9-111926389-C-A

Variant names:

• chr9-111926389-C-A
• NM_003358.3:c.451C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003358.3(UGCG):​c.451C>A​(p.Pro151Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,449,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UGCG NM_003358.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

Genes affected

UGCG (HGNC:12524): (UDP-glucose ceramide glucosyltransferase) This gene encodes an enzyme that catalyzes the first glycosylation step in the biosynthesis of glycosphingolipids, which are membrane components containing lipid and sugar moieties. The product of this reaction is glucosylceramide, which is the core structure of many glycosphingolipids. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGCG	NM_003358.3	c.451C>A	p.Pro151Thr	missense_variant	Exon 5 of 9	ENST00000374279.4	NP_003349.1
UGCG	XM_047423844.1	c.67C>A	p.Pro23Thr	missense_variant	Exon 5 of 9		XP_047279800.1
UGCG	XM_017015107.2	c.451C>A	p.Pro151Thr	missense_variant	Exon 5 of 6		XP_016870596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGCG	ENST00000374279.4	c.451C>A	p.Pro151Thr	missense_variant	Exon 5 of 9	1	NM_003358.3	ENSP00000363397.3
UGCG	ENST00000490110.5	n.544C>A		non_coding_transcript_exon_variant	Exon 6 of 6	3
UGCG	ENST00000495085.1	n.498C>A		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449588 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 720614

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451C>A (p.P151T) alteration is located in exon 5 (coding exon 5) of the UGCG gene. This alteration results from a C to A substitution at nucleotide position 451, causing the proline (P) at amino acid position 151 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.47
Sift	Benign	0.19	T
Sift4G	Benign	0.39	T
Polyphen		0.12	B
Vest4		0.70
MutPred		0.58		Gain of helix (P = 0.0325);
MVP		0.81
MPC		0.99
ClinPred		0.90	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr9-114688669;