chr2-85888869-G-A

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

2
2
14

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)

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 CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar as Benign. Clinvar id is 193261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85888869-G-A is described in CliVar 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
ST3GAL5NM_003896.4 linkc.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
ST3GAL5ENST00000638572.2 linkc.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.:
1
Cov.:
33
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.:
30
Cov.:
30
AF XY:
0.00625
AC XY:
3731
AN XY:
596516
show subpopulations
African (AFR)
AF:
0.000481
AC:
12
AN:
24926
American (AMR)
AF:
0.00367
AC:
82
AN:
22320
Ashkenazi Jewish (ASJ)
AF:
0.00273
AC:
54
AN:
19792
East Asian (EAS)
AF:
0.0000405
AC:
1
AN:
24712
South Asian (SAS)
AF:
0.0128
AC:
741
AN:
58088
European-Finnish (FIN)
AF:
0.000278
AC:
8
AN:
28738
Middle Eastern (MID)
AF:
0.00897
AC:
30
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
0
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
0
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.:
1
Cov.:
33
AF XY:
0.00346
AC XY:
256
AN XY:
74056
show subpopulations
African (AFR)
AF:
0.000988
AC:
41
AN:
41490
American (AMR)
AF:
0.00487
AC:
74
AN:
15202
Ashkenazi Jewish (ASJ)
AF:
0.00318
AC:
11
AN:
3464
East Asian (EAS)
AF:
0.000194
AC:
1
AN:
5164
South Asian (SAS)
AF:
0.00849
AC:
41
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10360
Middle Eastern (MID)
AF:
0.00685
AC:
2
AN:
292
European-Non Finnish (NFE)
AF:
0.00586
AC:
397
AN:
67776
Other (OTH)
AF:
0.00190
AC:
4
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
31
63
94
126
157
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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.:
0
Bravo
AF:
0.00357
ExAC
AF:
0.00934
AC:
116
Asia WGS
AF:
0.00372
AC:
12
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
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.;.
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.68
T;T;T
MetaRNN
Benign
0.0042
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.1
L;.;.
PhyloP100
0.11
PrimateAI
Uncertain
0.76
T
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
T
GERP RS
1.2
PromoterAI
0.047
Neutral
Varity_R
0.13
gMVP
0.25
Mutation Taster
=97/3
polymorphism

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

Other links and lift over

dbSNP: rs559756386; hg19: chr2-86115992; COSMIC: COSV106445819; COSMIC: COSV106445819; API