7-100160031-C-A

Variant names:

• chr7-100160031-C-A
• rs144461733
• NM_024637.5:c.1358G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024637.5(GAL3ST4):​c.1358G>T​(p.Arg453Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R453H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GAL3ST4 NM_024637.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789
• Publications: 0 publications found

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

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=0.35750157).

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.1358G>T	p.Arg453Leu	missense	Exon 4 of 4	NP_078913.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST4	ENST00000360039.9	TSL:1 MANE Select	c.1358G>T	p.Arg453Leu	missense	Exon 4 of 4	ENSP00000353142.4	Q96RP7-1
	GAL3ST4	ENST00000413800.5	TSL:1	c.1358G>T	p.Arg453Leu	missense	Exon 3 of 3	ENSP00000400451.1	Q96RP7-1
	GAL3ST4	ENST00000495882.1	TSL:1	n.2375G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 64 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.79
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.60		Loss of phosphorylation at T456 (P = 0.0474)
MVP		0.41
MPC		0.44
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.55
gMVP		0.75
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs144461733; hg19: chr7-99757654;