15-92438603-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006011.4(ST8SIA2):c.541G>A(p.Val181Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,606,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: ST8SIA2 NM_006011.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29299802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA2	NM_006011.4	c.541G>A	p.Val181Ile	missense_variant	4/6	ENST00000268164.8
ST8SIA2	NM_001330416.2	c.478G>A	p.Val160Ile	missense_variant	3/5
ST8SIA2	XM_017022642.2	c.604G>A	p.Val202Ile	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.541G>A	p.Val181Ile	missense_variant	4/6	1	NM_006011.4	P1
ST8SIA2	ENST00000539113.5	c.478G>A	p.Val160Ile	missense_variant	3/5	1
ST8SIA2	ENST00000555434.1	c.412G>A	p.Val138Ile	missense_variant	3/5	5
ST8SIA2	ENST00000556382.1	n.311G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000114 AC: 28 AN: 245002 Hom.: 0 AF XY: 0.0000906 AC XY: 12 AN XY: 132494

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.000445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000679

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000632

Gnomad OTH exome AF: 0.000504

GnomAD4 exome AF: 0.0000474 AC: 69 AN: 1454218 Hom.: 0 Cov.: 31 AF XY: 0.0000443 AC XY: 32 AN XY: 722416

Gnomad4 AFR exome AF: 0.0000605

Gnomad4 AMR exome AF: 0.000456

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000334

Gnomad4 OTH exome AF: 0.0000500

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74458

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000566 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000989 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.00

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

Sep 27, 2022

The c.541G>A (p.V181I) alteration is located in exon 4 (coding exon 4) of the ST8SIA2 gene. This alteration results from a G to A substitution at nucleotide position 541, causing the valine (V) at amino acid position 181 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.22
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T;T;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.93	N;N;N
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.49
MVP		0.37
MPC		1.3
ClinPred		0.15	T
GERP RS		4.1
Varity_R		0.37
gMVP		0.59

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: rs369258273; hg19: chr15-92981833;