rs6759239

Variant names:

• chr2-85858435-T-C
• rs6759239
• NM_003896.4:c.318+2746A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003896.4(ST3GAL5):​c.318+2746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,066 control chromosomes in the GnomAD database, including 7,667 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 0.31 (7667 hom., cov: 32)
• Consequence: ST3GAL5 NM_003896.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 3 publications found

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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	NM_003896.4	MANE Select	c.318+2746A>G		intron	N/A	NP_003887.3
	ST3GAL5	NM_001042437.2		c.249+2746A>G		intron	N/A	NP_001035902.1	Q9UNP4-3
	ST3GAL5	NM_001354227.2		c.234+2746A>G		intron	N/A	NP_001341156.1	A0A0S2Z4S6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	ENST00000638572.2	TSL:1 MANE Select	c.318+2746A>G		intron	N/A	ENSP00000491316.1	Q9UNP4-1
	ST3GAL5	ENST00000393808.8	TSL:1	c.249+2746A>G		intron	N/A	ENSP00000377397.3	Q9UNP4-3
	ST3GAL5	ENST00000393805.6	TSL:1	c.234+2746A>G		intron	N/A	ENSP00000377394.1	Q9UNP4-2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47065 AN: 151948 Hom.: 7663 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.310 AC: 47088 AN: 152066 Hom.: 7667 Cov.: 32 AF XY: 0.313 AC XY: 23259 AN XY: 74330

African (AFR) AF: 0.247 AC: 10262 AN: 41470

American (AMR) AF: 0.264 AC: 4037 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3468

East Asian (EAS) AF: 0.539 AC: 2790 AN: 5172

South Asian (SAS) AF: 0.439 AC: 2116 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3458 AN: 10566

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22563 AN: 67962

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.321 Hom.: 1036

Bravo AF: 0.298

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.31
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6759239; hg19: chr2-86085558;