7-100160331-C-T

Variant names:

• chr7-100160331-C-T
• rs3800952
• NM_024637.5:c.1058G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024637.5(GAL3ST4):​c.1058G>A​(p.Arg353Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,613,870 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R353W) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0018 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (67 hom.)
• Consequence: GAL3ST4 NM_024637.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.599

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017395914).
• BP6: Variant 7-100160331-C-T is Benign according to our data. Variant chr7-100160331-C-T is described in ClinVar as [Benign]. Clinvar id is 773744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL3ST4	NM_024637.5	c.1058G>A	p.Arg353Gln	missense_variant	Exon 4 of 4	ENST00000360039.9	NP_078913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAL3ST4	ENST00000360039.9	c.1058G>A	p.Arg353Gln	missense_variant	Exon 4 of 4	1	NM_024637.5	ENSP00000353142.4

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 276 AN: 152230 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00391 AC: 981 AN: 250636 Hom.: 18 AF XY: 0.00365 AC XY: 495 AN XY: 135544

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0519

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00168 AC: 2461 AN: 1461522 Hom.: 67 Cov.: 65 AF XY: 0.00165 AC XY: 1198 AN XY: 727044

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0576

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152348 Hom.: 7 Cov.: 32 AF XY: 0.00189 AC XY: 141 AN XY: 74490

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0494

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00101 Hom.: 3

Bravo AF: 0.00227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00414 AC: 503

Asia WGS AF: 0.00808 AC: 29 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.73
DEOGEN2	Benign	0.0014	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.27	.;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.025	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.015
Sift	Benign	1.0	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.017	B;B
Vest4		0.077
MVP		0.055
MPC		0.10
ClinPred		0.0032	T
GERP RS		-4.9
Varity_R		0.017
gMVP		0.13

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: rs3800952; hg19: chr7-99757954; COSMIC: COSV57585639; COSMIC: COSV57585639;