2-85848044-G-T

Position:

• chr2-85848044-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003896.4(ST3GAL5):​c.479C>A​(p.Pro160His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST3GAL5 NM_003896.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 6.84

Genes affected

ST3GAL5 (HGNC:10872): (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL5	NM_003896.4	c.479C>A	p.Pro160His	missense_variant	4/7	ENST00000638572.2	NP_003887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2	c.479C>A	p.Pro160His	missense_variant	4/7	1	NM_003896.4	ENSP00000491316.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GM3 synthase deficiency Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	Mar 23, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Baylor Genetics	Jun 30, 2020	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Research Center, Shahid Beheshti University of Medical Sciences	May 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;.;.;.;.;.;.;.;.;T;.;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;.;.;D;D;D;.;.;.;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Pathogenic	3.1	M;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.9	.;D;D;.;.;.;.;.;.;.;.;.;D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	.;D;D;.;.;.;.;.;.;.;.;.;D
Sift4G	Uncertain	0.0050	.;D;D;.;.;.;.;.;.;.;.;.;.
Polyphen		1.0	D;D;D;D;.;.;.;D;D;D;.;D;.
Vest4		0.68, 0.67
MutPred		0.73		Loss of catalytic residue at P160 (P = 0.0407);.;.;.;.;Loss of catalytic residue at P160 (P = 0.0407);.;.;.;.;.;.;.;
MVP		0.90
MPC		1.1
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.72
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553405319; hg19: chr2-86075167;