Variant 10-17321122-G-A 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.953C>T(p.Ala318Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ST8SIA6
NM_001004470.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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 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=0.057216555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA6	NM_001004470.3 linkuse as main transcript	c.953C>T	p.Ala318Val	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.953C>T	p.Ala318Val	missense_variant	8/8	1	NM_001004470.3	ENSP00000366827.4	P61647
ST8SIA6	ENST00000440449.5 linkuse as main transcript	c.345+68C>T		intron_variant		5		ENSP00000388343.1	H0Y405
ST8SIA6	ENST00000648997.1 linkuse as main transcript	n.*695C>T		non_coding_transcript_exon_variant	9/9			ENSP00000497856.1	A0A3B3ITM3
ST8SIA6	ENST00000648997.1 linkuse as main transcript	n.*695C>T		3_prime_UTR_variant	9/9			ENSP00000497856.1	A0A3B3ITM3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251064

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000979

Gnomad SAS 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:

0.00000821

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000302

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

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000769

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000824

AC:

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

Jan 04, 2024

The c.953C>T (p.A318V) alteration is located in exon 8 (coding exon 8) of the ST8SIA6 gene. This alteration results from a C to T substitution at nucleotide position 953, causing the alanine (A) at amino acid position 318 to be replaced by a valine (V). 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

-0.50

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

Eigen

Benign

0.052

Eigen_PC

Benign

0.019

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

M_CAP

Benign

0.013

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.080

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.010

Polyphen

0.72

Vest4

0.037

MutPred

0.52

Gain of MoRF binding (P = 0.0958);

MVP

0.28

MPC

0.076

ClinPred

0.29

GERP RS

3.5

Varity_R

0.17

gMVP

0.39

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