chr2-85863413-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_003896.4(ST3GAL5):c.155G>A(p.Arg52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,614,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

ST3GAL5
NM_003896.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.116

Publications

1 publications found

Variant links:

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]

ST3GAL5 Gene-Disease associations (from GenCC):

GM3 synthase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ST3GAL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006441742).

BP6

Variant 2-85863413-C-T is Benign according to our data. Variant chr2-85863413-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 464397.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00101 (154/152270) while in subpopulation AFR AF = 0.00289 (120/41534). AF 95% confidence interval is 0.00247. There are 1 homozygotes in GnomAd4. There are 77 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL5	NM_003896.4 link	c.155G>A	p.Arg52Gln	missense_variant	Exon 2 of 7	ENST00000638572.2	NP_003887.3	Q9UNP4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2 link	c.155G>A	p.Arg52Gln	missense_variant	Exon 2 of 7	1	NM_003896.4	ENSP00000491316.1		Q9UNP4-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000195

AC:

AN:

251476

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000903

AC:

132

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00281

AC:

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112010

Other (OTH)

AF:

0.000215

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152270

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41534

American (AMR)

AF:

0.00216

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000977

Hom.:

Bravo

AF:

0.00142

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000231

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Dec 27, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 26, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GM3 synthase deficiency

Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ST3GAL5-related disorder

Benign:1

Jun 06, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;.;.;.;.;.;.;.;.;.;T;.;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.83

T;T;.;.;T;T;T;.;.;.;T;T;T;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0064

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

N;.;.;.;.;.;.;.;.;.;.;.;.;.

PhyloP100

-0.12

PrimateAI

Benign

0.26

PROVEAN

Benign

0.040

.;N;N;.;N;.;.;.;.;.;.;.;N;.

REVEL

Benign

0.032

Sift

Benign

0.18

.;T;T;.;T;.;.;.;.;.;.;.;T;.

Sift4G

Benign

0.25

.;T;T;.;T;.;.;.;.;.;.;.;.;.

Polyphen

0.0070

B;B;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.14, 0.15, 0.14

MVP

0.067

MPC

0.35

ClinPred

0.0057

GERP RS

1.4

Varity_R

0.026

gMVP

0.15

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over