NM_003896.4:c.83-423G>A

Variant names:

• chr2-85863908-C-T
• rs6547635
• NM_003896.4:c.83-423G>A

Variant summary

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

The NM_003896.4(ST3GAL5):​c.83-423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 151,990 control chromosomes in the GnomAD database, including 1,032 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 0.11 (1032 hom., cov: 31)
• Consequence: ST3GAL5 NM_003896.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	NM_003896.4	MANE Select	c.83-423G>A		intron	N/A	NP_003887.3
	ST3GAL5	NM_001042437.2		c.14-423G>A		intron	N/A	NP_001035902.1
	ST3GAL5	NM_001354227.2		c.-2-423G>A		intron	N/A	NP_001341156.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL5	ENST00000638572.2	TSL:1 MANE Select	c.83-423G>A		intron	N/A	ENSP00000491316.1
	ST3GAL5	ENST00000393808.8	TSL:1	c.14-423G>A		intron	N/A	ENSP00000377397.3
	ST3GAL5	ENST00000393805.6	TSL:1	c.-2-423G>A		intron	N/A	ENSP00000377394.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17038 AN: 151872 Hom.: 1029 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.112 AC: 17055 AN: 151990 Hom.: 1032 Cov.: 31 AF XY: 0.111 AC XY: 8249 AN XY: 74296

African (AFR) AF: 0.109 AC: 4521 AN: 41468

American (AMR) AF: 0.0912 AC: 1392 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1194 AN: 5142

South Asian (SAS) AF: 0.0863 AC: 415 AN: 4808

European-Finnish (FIN) AF: 0.0840 AC: 889 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7972 AN: 67942

Other (OTH) AF: 0.119 AC: 251 AN: 2104

Alfa AF: 0.108 Hom.: 122

Bravo AF: 0.112

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.84
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6547635; hg19: chr2-86091031;