rs749600701

Variant names:

• chr15-92438417-C-A
• rs749600701
• NM_006011.4:c.355C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-92438417-C-A
• chr15-92438417-C-G
• chr15-92438417-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006011.4(ST8SIA2):​c.355C>A​(p.Pro119Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P119A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST8SIA2 NM_006011.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• Publications: 0 publications found

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]

ST8SIA2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA2	NM_006011.4	MANE Select	c.355C>A	p.Pro119Thr	missense	Exon 4 of 6	NP_006002.1	Q92186
	ST8SIA2	NM_001330416.2		c.292C>A	p.Pro98Thr	missense	Exon 3 of 5	NP_001317345.1	C6G488

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA2	ENST00000268164.8	TSL:1 MANE Select	c.355C>A	p.Pro119Thr	missense	Exon 4 of 6	ENSP00000268164.3	Q92186
	ST8SIA2	ENST00000539113.5	TSL:1	c.292C>A	p.Pro98Thr	missense	Exon 3 of 5	ENSP00000437382.1	C6G488
	ST8SIA2	ENST00000957924.1		c.475C>A	p.Pro159Thr	missense	Exon 5 of 7	ENSP00000627983.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.27
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.83
MutPred		0.72		Gain of sheet (P = 0.0827)
MVP		0.22
MPC		1.6
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.22
gMVP		0.66
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs749600701; hg19: chr15-92981647;