Genetic Variant ST8SIA4:p.Ser61Cys (chr5-100895717-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005668.6(ST8SIA4):c.182C>G(p.Ser61Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,742 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ST8SIA4
NM_005668.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

Variant links:

Genes affected

ST8SIA4 (HGNC:10871): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4) The protein encoded by this gene catalyzes the polycondensation of alpha-2,8-linked sialic acid required for the synthesis of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). The encoded protein, which is a member of glycosyltransferase family 29, is a type II membrane protein that may be present in the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ST8SIA4 links:

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ACMG classification

Classification made for transcript

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=0.33610788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA4	NM_005668.6 link	c.182C>G	p.Ser61Cys	missense_variant	Exon 2 of 5	ENST00000231461.10	NP_005659.1	Q92187-1
ST8SIA4	NM_175052.3 link	c.182C>G	p.Ser61Cys	missense_variant	Exon 2 of 3		NP_778222.1	Q92187-2
ST8SIA4	XM_005272078.4 link	c.182C>G	p.Ser61Cys	missense_variant	Exon 2 of 5		XP_005272135.1
ST8SIA4	XM_011543630.3 link	c.182C>G	p.Ser61Cys	missense_variant	Exon 2 of 4		XP_011541932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ST8SIA4	ENST00000231461.10 link	c.182C>G	p.Ser61Cys	missense_variant	Exon 2 of 5	1	NM_005668.6	ENSP00000231461.4	Q92187-1
ST8SIA4	ENST00000451528.2 link	c.182C>G	p.Ser61Cys	missense_variant	Exon 2 of 3	1		ENSP00000428914.1	Q92187-2
ST8SIA4	ENST00000523381.1 link	n.*190C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3		ENSP00000428826.1	E5RFK3
ST8SIA4	ENST00000523381.1 link	n.*190C>G		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000428826.1	E5RFK3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251026

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726680

show subpopulations

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.182C>G (p.S61C) alteration is located in exon 2 (coding exon 2) of the ST8SIA4 gene. This alteration results from a C to G substitution at nucleotide position 182, causing the serine (S) at amino acid position 61 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.023

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

1.0

D;.

Vest4

0.48

MutPred

0.58

Loss of disorder (P = 0.0081);Loss of disorder (P = 0.0081);

MVP

0.068

MPC

1.1

ClinPred

0.66

GERP RS

6.1

Varity_R

0.088

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over