2-85861188-T-C

Position:

chr2-85861188-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003896.4(ST3GAL5):c.311A>G(p.His104Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,594,414 control chromosomes in the GnomAD database, including 35,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2910 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32892 hom. )

Consequence

ST3GAL5
NM_003896.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.10

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035613477).

BP6

Variant 2-85861188-T-C is Benign according to our data. Variant chr2-85861188-T-C is described in ClinVar as [Benign]. Clinvar id is 130382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL5	NM_003896.4 linkuse as main transcript	c.311A>G	p.His104Arg	missense_variant	3/7	ENST00000638572.2	NP_003887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2 linkuse as main transcript	c.311A>G	p.His104Arg	missense_variant	3/7	1	NM_003896.4	ENSP00000491316	A1	Q9UNP4-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27292

AN:

152132

Hom.:

2913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0771

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.217

AC:

54473

AN:

251086

Hom.:

6505

AF XY:

0.226

AC XY:

30667

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0726

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.321

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.209

AC:

301568

AN:

1442164

Hom.:

32892

Cov.:

AF XY:

0.213

AC XY:

152873

AN XY:

718782

show subpopulations

Gnomad4 AFR exome

AF:

0.0707

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.179

AC:

27280

AN:

152250

Hom.:

2910

Cov.:

AF XY:

0.184

AC XY:

13729

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0769

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.214

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.198

Hom.:

6458

Bravo

AF:

0.165

TwinsUK

AF:

0.205

AC:

760

ALSPAC

AF:

0.214

AC:

826

ESP6500AA

AF:

0.0758

AC:

334

ESP6500EA

AF:

0.198

AC:

1705

ExAC

AF:

0.222

AC:

26999

Asia WGS

AF:

0.262

AC:

909

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.209

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

GM3 synthase deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 21, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 27, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.17

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

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.40

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

MetaRNN

Benign

0.0036

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

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

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

0.10

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

REVEL

Benign

0.082

Sift

Benign

1.0

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

Sift4G

Benign

0.69

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

Polyphen

0.0

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

Vest4

0.033, 0.018, 0.017

MPC

0.37

ClinPred

0.000012

GERP RS

5.0

Varity_R

0.039

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over