15-92438591-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006011.4(ST8SIA2):c.529G>T(p.Ala177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ST8SIA2 NM_006011.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

ST8SIA2 (HGNC:10870): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03758961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA2	NM_006011.4	c.529G>T	p.Ala177Ser	missense_variant	4/6	ENST00000268164.8
ST8SIA2	NM_001330416.2	c.466G>T	p.Ala156Ser	missense_variant	3/5
ST8SIA2	XM_017022642.2	c.592G>T	p.Ala198Ser	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.529G>T	p.Ala177Ser	missense_variant	4/6	1	NM_006011.4	P1
ST8SIA2	ENST00000539113.5	c.466G>T	p.Ala156Ser	missense_variant	3/5	1
ST8SIA2	ENST00000555434.1	c.400G>T	p.Ala134Ser	missense_variant	3/5	5
ST8SIA2	ENST00000556382.1	n.299G>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1456460 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 723768

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000722

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.529G>T (p.A177S) alteration is located in exon 4 (coding exon 4) of the ST8SIA2 gene. This alteration results from a G to T substitution at nucleotide position 529, causing the alanine (A) at amino acid position 177 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	9.0
Dann	Benign	0.18
DEOGEN2	Benign	0.081	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.84	N;.;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.6	N;N;N
REVEL	Benign	0.050
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.16
MutPred		0.56		Gain of disorder (P = 0.0345);.;.;
MVP		0.068
MPC		0.52
ClinPred		0.033	T
GERP RS		2.5
Varity_R		0.031
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs762911640; hg19: chr15-92981821;