NM_015879.3:c.488C>T

Variant names:

• chr18-57357098-C-T
• NM_015879.3:c.488C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015879.3(ST8SIA3):​c.488C>T​(p.Ala163Val) 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: 33)
• Consequence: ST8SIA3 NM_015879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55
• Publications: 0 publications found

Genes affected

ST8SIA3 (HGNC:14269): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 3) Enables alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity and identical protein binding activity. Involved in several processes, including ganglioside biosynthetic process; glycoprotein metabolic process; and protein sialylation. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293721 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015879.3. 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
	ST8SIA3	NM_015879.3	MANE Select	c.488C>T	p.Ala163Val	missense	Exon 3 of 4	NP_056963.2	O43173

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA3	ENST00000324000.4	TSL:1 MANE Select	c.488C>T	p.Ala163Val	missense	Exon 3 of 4	ENSP00000320431.2	O43173
	ENSG00000293721	ENST00000718553.1		n.60+66778G>A		intron	N/A
	ENSG00000293721	ENST00000718554.1		n.87-27614G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.83
MutPred		0.89		Gain of sheet (P = 0.0827)
MVP		0.24
MPC		1.3
ClinPred		0.98	D
GERP RS		6.0
PromoterAI		-0.0042	Neutral
Varity_R		0.83
gMVP		0.89

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

Other links and lift over

hg19: chr18-55024329;