Variant 10-17453563-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001004470.3(ST8SIA6):c.196A>T(p.Asn66Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ST8SIA6
NM_001004470.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity SIA8F_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA6	NM_001004470.3 linkuse as main transcript	c.196A>T	p.Asn66Tyr	missense_variant	2/8	ENST00000377602.5	NP_001004470.1	P61647
ST8SIA6	XM_017016174.2 linkuse as main transcript	c.196A>T	p.Asn66Tyr	missense_variant	2/7		XP_016871663.1
ST8SIA6	NM_001345961.2 linkuse as main transcript	c.-327A>T		5_prime_UTR_variant	2/9		NP_001332890.1
ST8SIA6	NR_144322.2 linkuse as main transcript	n.536A>T		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA6	ENST00000377602.5 linkuse as main transcript	c.196A>T	p.Asn66Tyr	missense_variant	2/8	1	NM_001004470.3	ENSP00000366827.4		P61647
ST8SIA6	ENST00000648997.1 linkuse as main transcript	n.136A>T		non_coding_transcript_exon_variant	2/9			ENSP00000497856.1		A0A3B3ITM3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1175164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

566686

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:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.196A>T (p.N66Y) alteration is located in exon 2 (coding exon 2) of the ST8SIA6 gene. This alteration results from a A to T substitution at nucleotide position 196, causing the asparagine (N) at amino acid position 66 to be replaced by a tyrosine (Y). 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

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0065

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.49

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.92

REVEL

Benign

0.073

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.017

Polyphen

0.98

Vest4

0.48

MutPred

0.23

Loss of disorder (P = 0.0339);

MVP

0.49

MPC

0.098

ClinPred

0.65

GERP RS

4.5

Varity_R

0.097

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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