Genetic Variant ST8SIA4:p.Asp220Ala (chr5-100856241-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005668.6(ST8SIA4):c.659A>C(p.Asp220Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ST8SIA4
NM_005668.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA4	NM_005668.6 link	c.659A>C	p.Asp220Ala	missense_variant	Exon 4 of 5	ENST00000231461.10	NP_005659.1	Q92187-1
ST8SIA4	XM_005272078.4 link	c.659A>C	p.Asp220Ala	missense_variant	Exon 4 of 5		XP_005272135.1
ST8SIA4	XM_011543630.3 link	c.503+30102A>C		intron_variant	Intron 3 of 3		XP_011541932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA4	ENST00000231461.10 link	c.659A>C	p.Asp220Ala	missense_variant	Exon 4 of 5	1	NM_005668.6	ENSP00000231461.4		Q92187-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727204

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659A>C (p.D220A) alteration is located in exon 4 (coding exon 4) of the ST8SIA4 gene. This alteration results from a A to C substitution at nucleotide position 659, causing the aspartic acid (D) at amino acid position 220 to be replaced by an alanine (A). 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

0.30

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0087

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.13

Sift

Benign

0.056

Sift4G

Uncertain

0.044

Polyphen

0.72

Vest4

0.55

MutPred

0.62

Loss of sheet (P = 0.0181);

MVP

0.068

MPC

0.64

ClinPred

0.88

GERP RS

5.3

Varity_R

0.42

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over