Genetic Variant ST3GAL5:c.318+2493G>A (chr2-85858688-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003896.4(ST3GAL5):c.318+2493G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,978 control chromosomes in the GnomAD database, including 23,777 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23777 hom., cov: 31)

Consequence

ST3GAL5
NM_003896.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ST3GAL5	NM_003896.4	MANE Select	c.318+2493G>A	intron	N/A	NP_003887.3
ST3GAL5	NM_001042437.2		c.249+2493G>A	intron	N/A	NP_001035902.1
ST3GAL5	NM_001354227.2		c.234+2493G>A	intron	N/A	NP_001341156.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ST3GAL5	ENST00000638572.2	TSL:1 MANE Select	c.318+2493G>A	intron	N/A	ENSP00000491316.1
ST3GAL5	ENST00000393808.8	TSL:1	c.249+2493G>A	intron	N/A	ENSP00000377397.3
ST3GAL5	ENST00000393805.6	TSL:1	c.234+2493G>A	intron	N/A	ENSP00000377394.1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84049

AN:

151860

Hom.:

23732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.554

AC:

84150

AN:

151978

Hom.:

23777

Cov.:

AF XY:

0.553

AC XY:

41081

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.615

AC:

25501

AN:

41466

American (AMR)

AF:

0.629

AC:

9611

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1543

AN:

3468

East Asian (EAS)

AF:

0.678

AC:

3496

AN:

5156

South Asian (SAS)

AF:

0.435

AC:

2092

AN:

4810

European-Finnish (FIN)

AF:

0.504

AC:

5316

AN:

10558

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34890

AN:

67936

Other (OTH)

AF:

0.541

AC:

1136

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1886

3772

5658

7544

9430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.477

Hom.:

2397

Bravo

AF:

0.570

Asia WGS

AF:

0.604

AC:

2099

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.12

(source)

DANN

Benign

0.32

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over