18-57353021-T-C

Variant names:

• chr18-57353021-T-C
• NM_015879.3:c.175T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015879.3(ST8SIA3):​c.175T>C​(p.Phe59Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ST8SIA3 NM_015879.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41432828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA3	NM_015879.3	c.175T>C	p.Phe59Leu	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.175T>C	p.Phe59Leu	missense_variant	Exon 1 of 4	1	NM_015879.3	ENSP00000320431.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454768 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175T>C (p.F59L) alteration is located in exon 1 (coding exon 1) of the ST8SIA3 gene. This alteration results from a T to C substitution at nucleotide position 175, causing the phenylalanine (F) at amino acid position 59 to be replaced by a leucine (L). 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	0.81
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.97	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.22
Sift	Benign	0.20	T
Sift4G	Benign	0.42	T
Polyphen		0.96	P
Vest4		0.56
MutPred		0.41		Gain of helix (P = 0.062);
MVP		0.23
MPC		0.65
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.30
gMVP		0.78

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: chr18-55020252;