dbSNP rs147924375: ST8SIA4:p.Gly354Ala (chr5-100811866-C-G) – 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.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

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=0.37463003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA4	NM_005668.6 link	c.1061G>C	p.Gly354Ala	missense_variant	Exon 5 of 5	ENST00000231461.10	NP_005659.1	Q92187-1
ST8SIA4	XM_011543630.3 link	c.767G>C	p.Gly256Ala	missense_variant	Exon 4 of 4		XP_011541932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA4	ENST00000231461.10 link	c.1061G>C	p.Gly354Ala	missense_variant	Exon 5 of 5	1	NM_005668.6	ENSP00000231461.4		Q92187-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250038

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135238

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:

0.0000329

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

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over