11-126408467-A-G

Variant names:

• chr11-126408467-A-G
• rs865787980
• NM_001254757.2:c.598A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001254757.2(ST3GAL4):​c.598A>G​(p.Ile200Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.8e-7 (0 hom.)
• Consequence: ST3GAL4 NM_001254757.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

Genes affected

ST3GAL4 (HGNC:10864): (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) This gene encodes a member of the glycosyltransferase 29 family, a group of enzymes involved in protein glycosylation. The encoded protein is targeted to Golgi membranes but may be proteolytically processed and secreted. The gene product may also be involved in the increased expression of sialyl Lewis X antigen seen in inflammatory responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25230926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL4	NM_001254757.2	c.598A>G	p.Ile200Val	missense_variant	Exon 8 of 11	ENST00000444328.7	NP_001241686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL4	ENST00000444328.7	c.598A>G	p.Ile200Val	missense_variant	Exon 8 of 11	5	NM_001254757.2	ENSP00000394354.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.586A>G (p.I196V) alteration is located in exon 8 (coding exon 7) of the ST3GAL4 gene. This alteration results from a A to G substitution at nucleotide position 586, causing the isoleucine (I) at amino acid position 196 to be replaced by a valine (V). 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	0.087
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;T;.;T;.;T;.;T;.;.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	.;.;D;.;T;.;D;D;D;D;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	.;L;.;L;.;L;.;L;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.77	N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.047
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;D;D;D;D;T
Sift4G	Uncertain	0.017	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.044	.;B;.;B;.;B;.;B;.;.;.;.
Vest4		0.065
MutPred		0.67		.;Loss of catalytic residue at I200 (P = 0.0926);.;Loss of catalytic residue at I200 (P = 0.0926);Loss of catalytic residue at I200 (P = 0.0926);Loss of catalytic residue at I200 (P = 0.0926);.;Loss of catalytic residue at I200 (P = 0.0926);.;.;.;.;
MVP		0.12
MPC		0.48
ClinPred		0.69	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.75

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: rs865787980; hg19: chr11-126278362;