rs3823646

chr7-100159989-G-Achr7-100159989-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024637.5(GAL3ST4):c.1400C>T(p.Ala467Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,612,990 control chromosomes in the GnomAD database, including 243,292 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.50 (19675 hom., cov: 30)
  • Exomes 𝑓: 0.55 (223617 hom.)
• Consequence: GAL3ST4 NM_024637.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.1614282E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAL3ST4	NM_024637.5	c.1400C>T	p.Ala467Val	missense_variant	4/4	ENST00000360039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAL3ST4	ENST00000360039.9	c.1400C>T	p.Ala467Val	missense_variant	4/4	1	NM_024637.5	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75970 AN: 151700 Hom.: 19661 Cov.: 30

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.512

GnomAD3 exomes AF: 0.540 AC: 135577 AN: 250978 Hom.: 37252 AF XY: 0.550 AC XY: 74628 AN XY: 135678

Gnomad AFR exome AF: 0.371

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.644

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.551 AC: 805340 AN: 1461172 Hom.: 223617 Cov.: 48 AF XY: 0.555 AC XY: 403087 AN XY: 726918

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.561

Gnomad4 NFE exome AF: 0.553

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.501 AC: 76025 AN: 151818 Hom.: 19675 Cov.: 30 AF XY: 0.505 AC XY: 37423 AN XY: 74174

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.512

Alfa AF: 0.548 Hom.: 57718

Bravo AF: 0.488

TwinsUK AF: 0.564 AC: 2093

ALSPAC AF: 0.549 AC: 2116

ESP6500AA AF: 0.386 AC: 1699

ESP6500EA AF: 0.568 AC: 4887

ExAC AF: 0.537 AC: 65198

Asia WGS AF: 0.606 AC: 2105 AN: 3478

EpiCase AF: 0.556

EpiControl AF: 0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0038	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.83	D
MetaRNN	Benign	0.0000062	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.071	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.024
Sift	Benign	0.041	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.0080	B;B
Vest4		0.027
MPC		0.11
ClinPred		0.0096	T
GERP RS		5.0
Varity_R		0.082
gMVP		0.46

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

Other links and lift over

dbSNP: rs3823646; hg19: chr7-99757612; COSMIC: COSV57586416; COSMIC: COSV57586416;