Genetic Variant GAL3ST4:p.His336Tyr (chr7-100160383-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024637.5(GAL3ST4):c.1006C>T(p.His336Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GAL3ST4
NM_024637.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.159

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 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=0.048675716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL3ST4	NM_024637.5 link	c.1006C>T	p.His336Tyr	missense_variant	Exon 4 of 4	ENST00000360039.9	NP_078913.3	Q96RP7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAL3ST4	ENST00000360039.9 link	c.1006C>T	p.His336Tyr	missense_variant	Exon 4 of 4	1	NM_024637.5	ENSP00000353142.4		Q96RP7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

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

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1006C>T (p.H336Y) alteration is located in exon 4 (coding exon 3) of the GAL3ST4 gene. This alteration results from a C to T substitution at nucleotide position 1006, causing the histidine (H) at amino acid position 336 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

0.094

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.4

DANN

Benign

0.68

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.0050

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.13

B;B

Vest4

0.11

MutPred

0.43

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);

MVP

0.13

MPC

0.13

ClinPred

0.10

GERP RS

0.41

Varity_R

0.056

gMVP

0.17

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

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