rs7561062

Variant names:

• chr2-85860049-T-A
• rs7561062
• NM_003896.4:c.318+1132A>T

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+1132A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,102 control chromosomes in the GnomAD database, including 7,534 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 (7534 hom., cov: 32)
• Consequence: ST3GAL5 NM_003896.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL5	NM_003896.4	c.318+1132A>T		intron_variant	Intron 3 of 6	ENST00000638572.2	NP_003887.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL5	ENST00000638572.2	c.318+1132A>T		intron_variant	Intron 3 of 6	1	NM_003896.4	ENSP00000491316.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46523 AN: 151984 Hom.: 7531 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.306 AC: 46538 AN: 152102 Hom.: 7534 Cov.: 32 AF XY: 0.309 AC XY: 22995 AN XY: 74350

African (AFR) AF: 0.235 AC: 9770 AN: 41502

American (AMR) AF: 0.262 AC: 4009 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2798 AN: 5176

South Asian (SAS) AF: 0.438 AC: 2109 AN: 4816

European-Finnish (FIN) AF: 0.327 AC: 3464 AN: 10586

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

European-Non Finnish (NFE) AF: 0.332 AC: 22531 AN: 67956

Other (OTH) AF: 0.320 AC: 673 AN: 2106

Alfa AF: 0.319 Hom.: 1030

Bravo AF: 0.294

Asia WGS AF: 0.455 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.42
PhyloP100		-0.50
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: rs7561062; hg19: chr2-86087172;