rs141917910

Variant names:

• chr2-85863413-C-T
• rs141917910
• NM_003896.4:c.155G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS1

The NM_003896.4(ST3GAL5):​c.155G>A​(p.Arg52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,614,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: ST3GAL5 NM_003896.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -0.116
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006441742).
• BP6: Variant 2-85863413-C-T is Benign according to our data. Variant chr2-85863413-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 464397.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00101 (154/152270) while in subpopulation AFR AF = 0.00289 (120/41534). AF 95% confidence interval is 0.00247. There are 1 homozygotes in GnomAd4. There are 77 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.155G>A	p.Arg52Gln	missense	Exon 2 of 7	NP_003887.3
	ST3GAL5	NM_001042437.2		c.86G>A	p.Arg29Gln	missense	Exon 2 of 7	NP_001035902.1	Q9UNP4-3
	ST3GAL5	NM_001354227.2		c.71G>A	p.Arg24Gln	missense	Exon 3 of 8	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.155G>A	p.Arg52Gln	missense	Exon 2 of 7	ENSP00000491316.1	Q9UNP4-1
	ST3GAL5	ENST00000393808.8	TSL:1	c.86G>A	p.Arg29Gln	missense	Exon 2 of 7	ENSP00000377397.3	Q9UNP4-3
	ST3GAL5	ENST00000393805.6	TSL:1	c.71G>A	p.Arg24Gln	missense	Exon 2 of 7	ENSP00000377394.1	Q9UNP4-2

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 154 AN: 152152 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000195 AC: 49 AN: 251476 AF XY: 0.000162

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000903 AC: 132 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.0000701 AC XY: 51 AN XY: 727246

African (AFR) AF: 0.00281 AC: 94 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112010

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152270 Hom.: 1 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74458

African (AFR) AF: 0.00289 AC: 120 AN: 41534

American (AMR) AF: 0.00216 AC: 33 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000977 Hom.: 0

Bravo AF: 0.00142

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000231 AC: 28

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	-	1	GM3 synthase deficiency (1)
-	-	1	ST3GAL5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.66	N
PhyloP100		-0.12
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.032
Sift	Benign	0.18	T
Sift4G	Benign	0.25	T
Polyphen		0.0070	B
Vest4		0.14
MVP		0.067
MPC		0.35
ClinPred		0.0057	T
GERP RS		1.4
Varity_R		0.026
gMVP		0.15
Mutation Taster		=97/3	polymorphism

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: rs141917910; hg19: chr2-86090536;