15-92464206-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006011.4(ST8SIA2):​c.949C>G​(p.Pro317Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

ST8SIA2
NM_006011.4 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.72
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST8SIA2NM_006011.4 linkc.949C>G p.Pro317Ala missense_variant Exon 6 of 6 ENST00000268164.8 NP_006002.1 Q92186B2R9U8
ST8SIA2NM_001330416.2 linkc.886C>G p.Pro296Ala missense_variant Exon 5 of 5 NP_001317345.1 C6G488B2R9U8Q4VAY9
ST8SIA2XM_017022642.2 linkc.1012C>G p.Pro338Ala missense_variant Exon 6 of 6 XP_016878131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ST8SIA2ENST00000268164.8 linkc.949C>G p.Pro317Ala missense_variant Exon 6 of 6 1 NM_006011.4 ENSP00000268164.3 Q92186
ST8SIA2ENST00000539113.5 linkc.886C>G p.Pro296Ala missense_variant Exon 5 of 5 1 ENSP00000437382.1 C6G488
ST8SIA2ENST00000555434.1 linkc.820C>G p.Pro274Ala missense_variant Exon 5 of 5 5 ENSP00000450851.1 G3V2T1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.949C>G (p.P317A) alteration is located in exon 6 (coding exon 6) of the ST8SIA2 gene. This alteration results from a C to G substitution at nucleotide position 949, causing the proline (P) at amino acid position 317 to be replaced by an alanine (A). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
T;.;.
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Benign
0.056
D
MetaRNN
Pathogenic
0.94
D;D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Pathogenic
2.9
M;.;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-7.7
D;D;D
REVEL
Uncertain
0.58
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.76
MutPred
0.84
Loss of sheet (P = 0.0817);.;.;
MVP
0.57
MPC
1.5
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.79
gMVP
0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-93007436; API