rs113976691

chr2-85844559-G-Achr2-85844559-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_003896.4(ST3GAL5):c.850-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,614,056 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: ST3GAL5 NM_003896.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002440
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.994

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-85844559-G-A is Benign according to our data. Variant chr2-85844559-G-A is described in ClinVar as [Benign]. Clinvar id is 239584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00381 (580/152218) while in subpopulation AFR AF= 0.0129 (536/41524). AF 95% confidence interval is 0.012. There are 1 homozygotes in gnomad4. There are 275 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.850-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000638572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL5	ENST00000638572.2	c.850-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003896.4	A1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 570 AN: 152100 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.000948 AC: 238 AN: 251146 Hom.: 1 AF XY: 0.000582 AC XY: 79 AN XY: 135798

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000809

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000390 AC: 570 AN: 1461838 Hom.: 2 Cov.: 31 AF XY: 0.000341 AC XY: 248 AN XY: 727226

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000638

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.00381 AC: 580 AN: 152218 Hom.: 1 Cov.: 32 AF XY: 0.00369 AC XY: 275 AN XY: 74436

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00129 Hom.: 0

Bravo AF: 0.00433

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GM3 synthase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Oct 05, 2017

- -

ST3GAL5-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.7
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.044
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

Other links and lift over

dbSNP: rs113976691; hg19: chr2-86071682;