chr2-85888869-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003896.4(ST3GAL5):c.37C>T(p.Pro13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00567 in 1,366,398 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P13T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 30 hom. )

Consequence

ST3GAL5
NM_003896.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.114

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004235208).

BP6

Variant 2-85888869-G-A is Benign according to our data. Variant chr2-85888869-G-A is described in ClinVar as [Benign]. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00377 (571/151588) while in subpopulation SAS AF = 0.00849 (41/4828). AF 95% confidence interval is 0.00643. There are 1 homozygotes in GnomAd4. There are 256 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL5	NM_003896.4 link	c.37C>T	p.Pro13Ser	missense_variant	Exon 1 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.37C>T	p.Pro13Ser	missense_variant	Exon 1 of 7	1	NM_003896.4	ENSP00000491316.1		Q9UNP4-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

569

AN:

151480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000991

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00487

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00584

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00568

AC:

381

AN:

67032

AF XY:

0.00679

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00331

Gnomad ASJ exome

AF:

0.00263

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00591

AC:

7183

AN:

1214810

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

3731

AN XY:

596516

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

24926

American (AMR)

AF:

0.00367

AC:

AN:

22320

Ashkenazi Jewish (ASJ)

AF:

0.00273

AC:

AN:

19792

East Asian (EAS)

AF:

0.0000405

AC:

AN:

24712

South Asian (SAS)

AF:

0.0128

AC:

741

AN:

58088

European-Finnish (FIN)

AF:

0.000278

AC:

AN:

28738

Middle Eastern (MID)

AF:

0.00897

AC:

AN:

3344

European-Non Finnish (NFE)

AF:

0.00606

AC:

5969

AN:

984676

Other (OTH)

AF:

0.00593

AC:

286

AN:

48214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

398

797

1195

1594

1992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.00377

AC:

571

AN:

151588

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

256

AN XY:

74056

show subpopulations

African (AFR)

AF:

0.000988

AC:

AN:

41490

American (AMR)

AF:

0.00487

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00318

AC:

AN:

3464

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.00849

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10360

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00586

AC:

397

AN:

67776

Other (OTH)

AF:

0.00190

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00160

Hom.:

Bravo

AF:

0.00357

ExAC

AF:

0.00934

AC:

116

Asia WGS

AF:

0.00372

AC:

AN:

3238

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

GM3 synthase deficiency

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 02, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Sep 29, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ST3GAL5: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Aug 15, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

0.11

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.86

.;N;.

REVEL

Benign

0.033

Sift

Pathogenic

0.0

.;D;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

0.0030

B;.;.

Vest4

0.15

MVP

0.099

MPC

0.31

ClinPred

0.018

GERP RS

1.2

PromoterAI

0.047

Neutral

(source)

Varity_R

0.13

gMVP

0.25

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