15-92464367-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006011.4(ST8SIA2):c.1110G>T(p.Gln370His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: ST8SIA2 NM_006011.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.013772488).
• BP6: Variant 15-92464367-G-T is Benign according to our data. Variant chr15-92464367-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038637.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST8SIA2	NM_006011.4	c.1110G>T	p.Gln370His	missense_variant	6/6	ENST00000268164.8
ST8SIA2	NM_001330416.2	c.1047G>T	p.Gln349His	missense_variant	5/5
ST8SIA2	XM_017022642.2	c.1173G>T	p.Gln391His	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.1110G>T	p.Gln370His	missense_variant	6/6	1	NM_006011.4	P1
ST8SIA2	ENST00000539113.5	c.1047G>T	p.Gln349His	missense_variant	5/5	1
ST8SIA2	ENST00000555434.1	c.981G>T	p.Gln327His	missense_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.000867 AC: 132 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

GnomAD3 exomes AF: 0.000211 AC: 53 AN: 251452 Hom.: 0 AF XY: 0.000177 AC XY: 24 AN XY: 135896

Gnomad AFR exome AF: 0.00289

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000869 AC: 127 AN: 1461594 Hom.: 0 Cov.: 35 AF XY: 0.0000605 AC XY: 44 AN XY: 727100

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.0000224

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: 0.0000162

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000873 AC: 133 AN: 152280 Hom.: 0 Cov.: 31 AF XY: 0.000819 AC XY: 61 AN XY: 74460

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000194 Hom.: 0

Bravo AF: 0.000922

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000288 AC: 35

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ST8SIA2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 27, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.014	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N;.;.
MutationTaster	Benign	0.60	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.64	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.42	T;T;D
Sift4G	Benign	0.25	T;T;T
Polyphen		0.027	B;B;.
Vest4		0.037
MutPred		0.43		Gain of glycosylation at T375 (P = 0.102);.;.;
MVP		0.093
MPC		0.80
ClinPred		0.023	T
GERP RS		4.7
Varity_R		0.049
gMVP		0.33

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: rs141226307; hg19: chr15-93007597;