Genetic Variant GAL3ST4:p.Lys468Asn (chr7-100159985-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024637.5(GAL3ST4):c.1404G>C(p.Lys468Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

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

Consequence

GAL3ST4
NM_024637.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.446

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27124625).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024637.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST4	NM_024637.5	MANE Select	c.1404G>C	p.Lys468Asn	missense	Exon 4 of 4	NP_078913.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAL3ST4	ENST00000360039.9	TSL:1 MANE Select	c.1404G>C	p.Lys468Asn	missense	Exon 4 of 4	ENSP00000353142.4	Q96RP7-1
GAL3ST4	ENST00000413800.5	TSL:1	c.1404G>C	p.Lys468Asn	missense	Exon 3 of 3	ENSP00000400451.1	Q96RP7-1
GAL3ST4	ENST00000495882.1	TSL:1	n.2421G>C		non_coding_transcript_exon	Exon 3 of 3

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

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41398

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0060

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

M_CAP

Benign

0.016

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-0.45

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Benign

0.11

Sift4G

Uncertain

0.043

Polyphen

1.0

Vest4

0.20

MutPred

0.50

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

Mutation Taster

=62/38

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over