18-57352991-G-C

Variant names:

• chr18-57352991-G-C
• NM_015879.3:c.145G>C

Variant summary

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

The NM_015879.3(ST8SIA3):​c.145G>C​(p.Ala49Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: ST8SIA3 NM_015879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.94

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]

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=0.118621945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA3	NM_015879.3	c.145G>C	p.Ala49Pro	missense_variant	Exon 1 of 4	ENST00000324000.4	NP_056963.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA3	ENST00000324000.4	c.145G>C	p.Ala49Pro	missense_variant	Exon 1 of 4	1	NM_015879.3	ENSP00000320431.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.145G>C (p.A49P) alteration is located in exon 1 (coding exon 1) of the ST8SIA3 gene. This alteration results from a G to C substitution at nucleotide position 145, causing the alanine (A) at amino acid position 49 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	Benign	0.093
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.037
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.086
Sift	Benign	0.20	T
Sift4G	Benign	0.20	T
Polyphen		0.19	B
Vest4		0.23
MutPred		0.29		Gain of loop (P = 0.0045);
MVP		0.11
MPC		0.67
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.28
gMVP		0.86

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: chr18-55020222;