rs199590656
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_003896.4(ST3GAL5):c.465G>A(p.Glu155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
ST3GAL5
NM_003896.4 synonymous
NM_003896.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.407
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 2-85848058-C-T is Benign according to our data. Variant chr2-85848058-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 282731.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
BP7
?
Synonymous conserved (PhyloP=-0.407 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000295 (45/152306) while in subpopulation EAS AF= 0.00732 (38/5190). AF 95% confidence interval is 0.00548. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL5 | NM_003896.4 | c.465G>A | p.Glu155= | synonymous_variant | 4/7 | ENST00000638572.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL5 | ENST00000638572.2 | c.465G>A | p.Glu155= | synonymous_variant | 4/7 | 1 | NM_003896.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000457 AC: 115AN: 251480Hom.: 0 AF XY: 0.000383 AC XY: 52AN XY: 135912
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GnomAD4 exome AF: 0.000178 AC: 260AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 127AN XY: 727248
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GnomAD4 genome ? AF: 0.000295 AC: 45AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74468
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
GM3 synthase deficiency Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 19, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at