NM_001254757.2:c.239C>A

Variant names:

• chr11-126407308-C-A
• rs751179970
• NM_001254757.2:c.239C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001254757.2(ST3GAL4):​c.239C>A​(p.Thr80Lys) 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 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. T80M) has been classified 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: 1.43
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20972544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001254757.2. 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
	ST3GAL4	NM_001254757.2	MANE Select	c.239C>A	p.Thr80Lys	missense	Exon 5 of 11	NP_001241686.1	Q11206-1
	ST3GAL4	NM_001348396.2		c.302C>A	p.Thr101Lys	missense	Exon 6 of 12	NP_001335325.1	A0A7P0RGI5
	ST3GAL4	NM_001348397.2		c.302C>A	p.Thr101Lys	missense	Exon 6 of 12	NP_001335326.1	A0A7P0RGI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL4	ENST00000444328.7	TSL:5 MANE Select	c.239C>A	p.Thr80Lys	missense	Exon 5 of 11	ENSP00000394354.2	Q11206-1
	ST3GAL4	ENST00000392669.6	TSL:1	c.239C>A	p.Thr80Lys	missense	Exon 5 of 11	ENSP00000376437.2	Q11206-1
	ST3GAL4	ENST00000526727.5	TSL:1	c.239C>A	p.Thr80Lys	missense	Exon 4 of 10	ENSP00000436047.1	Q11206-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 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: 53416

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
PhyloP100		1.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.27
Sift	Benign	0.71	T
Sift4G	Benign	0.95	T
Polyphen		0.046	B
Vest4		0.34
MutPred		0.72		Gain of ubiquitination at T80 (P = 0.0276)
MVP		0.19
MPC		0.67
ClinPred		0.64	D
GERP RS		3.9
Varity_R		0.046
gMVP		0.65
Mutation Taster		=83/17	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: rs751179970; hg19: chr11-126277203;