rs2298475

Positions:

• chr11-126408308-T-A
• chr11-126408308-T-C

Variant summary

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

The NM_001254757.2(ST3GAL4):​c.439T>A​(p.Leu147Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST3GAL4 NM_001254757.2 missense, splice_region
• Scores: Splicing: ADA: 0.001583
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

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 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
ST3GAL4	NM_001254757.2	c.439T>A	p.Leu147Met	missense_variant, splice_region_variant	8/11	ENST00000444328.7	NP_001241686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST3GAL4	ENST00000444328.7	c.439T>A	p.Leu147Met	missense_variant, splice_region_variant	8/11	5	NM_001254757.2	ENSP00000394354	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.10	.;T;.;T;.;T;.;T;.;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.82	.;.;T;.;T;.;T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	.;L;.;L;.;L;.;L;.;.;.
MutationTaster	Benign	5.3e-12	P;P;P;P;P;P;P;P;P;P
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.45	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.48	T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T;T;T;T;T
Polyphen		1.0	.;D;.;D;.;D;.;D;.;.;.
Vest4		0.50
MutPred		0.79		.;Gain of catalytic residue at V143 (P = 0.0478);.;Gain of catalytic residue at V143 (P = 0.0478);Gain of catalytic residue at V143 (P = 0.0478);Gain of catalytic residue at V143 (P = 0.0478);.;Gain of catalytic residue at V143 (P = 0.0478);.;.;.;
MVP		0.081
MPC		1.5
ClinPred		0.43	T
GERP RS		-5.7
Varity_R		0.063
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.30
SpliceAI score (max)		0.010		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: rs2298475; hg19: chr11-126278203;