7-100160484-A-G

Position:

• chr7-100160484-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024637.5(GAL3ST4):​c.905T>C​(p.Met302Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GAL3ST4 NM_024637.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAL3ST4	NM_024637.5	c.905T>C	p.Met302Thr	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	c.905T>C	p.Met302Thr	missense_variant	4/4	1	NM_024637.5	ENSP00000353142	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.905T>C (p.M302T) alteration is located in exon 4 (coding exon 3) of the GAL3ST4 gene. This alteration results from a T to C substitution at nucleotide position 905, causing the methionine (M) at amino acid position 302 to be replaced by a threonine (T). 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	0.79
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	0.92	D;D;D;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.081	B;B
Vest4		0.66
MutPred		0.83		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.32
MPC		0.22
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.86
gMVP		0.74

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.

Other links and lift over

hg19: chr7-99758107;