Variant 3-98793678-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001323368.2(ST3GAL6):c.913G>A(p.Ala305Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000754 in 1,577,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

ST3GAL6
NM_001323368.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Variant links:

Genes affected

ST3GAL6 (HGNC:18080): (ST3 beta-galactoside alpha-2,3-sialyltransferase 6) The protein encoded by this gene is a member of the sialyltransferase family. Members of this family are enzymes that transfer sialic acid from the activated cytidine 5'-monophospho-N-acetylneuraminic acid to terminal positions on sialylated glycolipids (gangliosides) or to the N- or O-linked sugar chains of glycoproteins. This protein has high specificity for neolactotetraosylceramide and neolactohexaosylceramide as glycolipid substrates and may contribute to the formation of selectin ligands and sialyl Lewis X, a carbohydrate important for cell-to-cell recognition and a blood group antigen. [provided by RefSeq, Apr 2016]

ST3GAL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11074439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST3GAL6	NM_001323368.2 link	c.913G>A	p.Ala305Thr	missense_variant	10/10	ENST00000483910.6	NP_001310297.1	Q9Y274-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL6	ENST00000483910.6 link	c.913G>A	p.Ala305Thr	missense_variant	10/10	1	NM_001323368.2	ENSP00000417376.1		Q9Y274-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000744

AC:

AN:

228342

Hom.:

AF XY:

0.0000728

AC XY:

AN XY:

123650

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000363

Gnomad ASJ exome

AF:

0.000424

Gnomad EAS exome

AF:

0.000120

Gnomad SAS exome

AF:

0.0000396

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000836

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000779

AC:

111

AN:

1425336

Hom.:

Cov.:

AF XY:

0.0000720

AC XY:

AN XY:

707844

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

Gnomad4 AMR exome

AF:

0.000104

Gnomad4 ASJ exome

AF:

0.000314

Gnomad4 EAS exome

AF:

0.0000522

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000812

Gnomad4 OTH exome

AF:

0.0000678

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

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

Nov 15, 2024

The c.913G>A (p.A305T) alteration is located in exon 11 (coding exon 9) of the ST3GAL6 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the alanine (A) at amino acid position 305 to be replaced by a threonine (T). 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

0.088

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.020

.;T;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

D;.;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.91

.;L;L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

0.31

N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.17

T;T;T;.

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.45

.;B;B;.

Vest4

0.16

MVP

0.29

MPC

0.22

ClinPred

0.055

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.52

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