Variant 7-100159985-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000360039.9(GAL3ST4):c.1404G>T(p.Lys468Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

GAL3ST4
ENST00000360039.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.446

Variant links:

Genes affected

GAL3ST4 (HGNC:24145): (galactose-3-O-sulfotransferase 4) This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate to the C-3' position of galactose residues in O-linked glycoproteins. This enzyme is highly specific for core 1 structures, with asialofetuin, Gal-beta-1,3-GalNAc and Gal-beta-1,3 (GlcNAc-beta-1,6)GalNAc being good substrates. [provided by RefSeq, Jul 2008]

GAL3ST4 links:

Genome browser will be placed here

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=0.2807545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAL3ST4	NM_024637.5 linkuse as main transcript	c.1404G>T	p.Lys468Asn	missense_variant	4/4	ENST00000360039.9	NP_078913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAL3ST4	ENST00000360039.9 linkuse as main transcript	c.1404G>T	p.Lys468Asn	missense_variant	4/4	1	NM_024637.5	ENSP00000353142	P1	Q96RP7-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152078

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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 10, 2022

The c.1404G>T (p.K468N) alteration is located in exon 4 (coding exon 3) of the GAL3ST4 gene. This alteration results from a G to T substitution at nucleotide position 1404, causing the lysine (K) at amino acid position 468 to be replaced by an asparagine (N). 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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0060

T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.10

Sift

Benign

0.11

T;T

Sift4G

Uncertain

0.043

D;D

Polyphen

1.0

D;D

Vest4

0.20

MutPred

0.50

Loss of ubiquitination at K468 (P = 0.0022);Loss of ubiquitination at K468 (P = 0.0022);

MVP

0.42

MPC

0.51

ClinPred

0.86

GERP RS

2.9

Varity_R

0.14

gMVP

0.73

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