15-92464206-C-G

Variant names:

• chr15-92464206-C-G
• NM_006011.4:c.949C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.72

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 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
ST8SIA2	NM_006011.4	c.949C>G	p.Pro317Ala	missense_variant	Exon 6 of 6	ENST00000268164.8	NP_006002.1
ST8SIA2	NM_001330416.2	c.886C>G	p.Pro296Ala	missense_variant	Exon 5 of 5		NP_001317345.1
ST8SIA2	XM_017022642.2	c.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
ST8SIA2	ENST00000268164.8	c.949C>G	p.Pro317Ala	missense_variant	Exon 6 of 6	1	NM_006011.4	ENSP00000268164.3
ST8SIA2	ENST00000539113.5	c.886C>G	p.Pro296Ala	missense_variant	Exon 5 of 5	1		ENSP00000437382.1
ST8SIA2	ENST00000555434.1	c.820C>G	p.Pro274Ala	missense_variant	Exon 5 of 5	5		ENSP00000450851.1

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

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;