dbSNP rs147924375: ST8SIA4:p.Gly354Ala (chr5-100811866-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005668.6(ST8SIA4):c.1061G>C(p.Gly354Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000959 in 1,459,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G354E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ST8SIA4
NM_005668.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.63

Publications

4 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37463003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005668.6. 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
	ST8SIA4	NM_005668.6	MANE Select	c.1061G>C	p.Gly354Ala	missense	Exon 5 of 5	NP_005659.1	Q92187-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ST8SIA4	ENST00000231461.10	TSL:1 MANE Select	c.1061G>C	p.Gly354Ala	missense	Exon 5 of 5	ENSP00000231461.4	Q92187-1
ST8SIA4	ENST00000956904.1		c.929G>C	p.Gly310Ala	missense	Exon 4 of 4	ENSP00000626963.1
ST8SIA4	ENST00000881366.1		c.803G>C	p.Gly268Ala	missense	Exon 4 of 4	ENSP00000551425.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250038

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459938

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

44406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111184

Other (OTH)

AF:

0.00

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.020

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

2.9

PhyloP100

3.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.6

REVEL

Benign

0.25

Sift

Benign

0.042

Sift4G

Benign

0.15

Polyphen

0.32

Vest4

0.59

MutPred

0.54

Loss of stability (P = 0.0898)

MVP

0.082

MPC

0.64

ClinPred

0.47

GERP RS

5.7

Varity_R

0.21

gMVP

0.82

Mutation Taster

=25/75

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over