Variant 10-17321213-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004470.3(ST8SIA6):c.862G>A(p.Glu288Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

ST8SIA6
NM_001004470.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.760

Variant links:

Genes affected

ST8SIA6 (HGNC:23317): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 6) This gene encodes a member of the glycosyltransferase 29 protein family. Members of this protein family synthesize sialylglycoconjugates. Sialylation may contribute to multidrug resistance in cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ST8SIA6 links:

ST8SIA6 (HGNC:):

ST8SIA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03110227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA6	NM_001004470.3 linkuse as main transcript	c.862G>A	p.Glu288Lys	missense_variant	8/8	ENST00000377602.5	NP_001004470.1	P61647

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ST8SIA6	ENST00000377602.5 linkuse as main transcript	c.862G>A	p.Glu288Lys	missense_variant	8/8	1	NM_001004470.3	ENSP00000366827.4	P61647
ST8SIA6	ENST00000440449.5 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	3/4	5		ENSP00000388343.1	H0Y405
ST8SIA6	ENST00000648997.1 linkuse as main transcript	n.*604G>A		non_coding_transcript_exon_variant	9/9			ENSP00000497856.1	A0A3B3ITM3
ST8SIA6	ENST00000648997.1 linkuse as main transcript	n.*604G>A		3_prime_UTR_variant	9/9			ENSP00000497856.1	A0A3B3ITM3

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251030

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000706

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000895

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:

0.0000603

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000602

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.7

DANN

Benign

0.17

DEOGEN2

Benign

0.019

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.68

M_CAP

Benign

0.0032

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.38

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.9

REVEL

Benign

0.080

Sift

Benign

0.98

Sift4G

Benign

0.82

Polyphen

0.0040

Vest4

0.027

MutPred

0.41

Gain of ubiquitination at E288 (P = 0.0238);

MVP

0.18

MPC

0.042

ClinPred

0.016

GERP RS

1.4

Varity_R

0.042

gMVP

0.54

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