15-92464216-T-C

Position:

• chr15-92464216-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000268164.8(ST8SIA2):​c.959T>C​(p.Leu320Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ST8SIA2 ENST00000268164.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10896799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA2	NM_006011.4	c.959T>C	p.Leu320Pro	missense_variant	6/6	ENST00000268164.8	NP_006002.1
ST8SIA2	NM_001330416.2	c.896T>C	p.Leu299Pro	missense_variant	5/5		NP_001317345.1
ST8SIA2	XM_017022642.2	c.1022T>C	p.Leu341Pro	missense_variant	6/6		XP_016878131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.959T>C	p.Leu320Pro	missense_variant	6/6	1	NM_006011.4	ENSP00000268164	P1
ST8SIA2	ENST00000539113.5	c.896T>C	p.Leu299Pro	missense_variant	5/5	1		ENSP00000437382
ST8SIA2	ENST00000555434.1	c.830T>C	p.Leu277Pro	missense_variant	5/5	5		ENSP00000450851

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.959T>C (p.L320P) alteration is located in exon 6 (coding exon 6) of the ST8SIA2 gene. This alteration results from a T to C substitution at nucleotide position 959, causing the leucine (L) at amino acid position 320 to be replaced by a proline (P). 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	0.91
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.097
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.056	B;B;.
Vest4		0.49
MutPred		0.45		Gain of disorder (P = 0.0099);.;.;
MVP		0.24
MPC		1.1
ClinPred		0.21	T
GERP RS		4.7
Varity_R		0.31
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-93007446;