chr11-126407259-C-T

Variant names:

• chr11-126407259-C-T
• rs765929837
• NM_001254757.2:c.190C>T

Variant summary

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

The NM_001254757.2(ST3GAL4):​c.190C>T​(p.Arg64Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R64Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ST3GAL4 NM_001254757.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 1 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 2 ACMG points.

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

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.190C>T	p.Arg64Trp	missense	Exon 5 of 11	NP_001241686.1	Q11206-1
	ST3GAL4	NM_001348396.2		c.253C>T	p.Arg85Trp	missense	Exon 6 of 12	NP_001335325.1	A0A7P0RGI5
	ST3GAL4	NM_001348397.2		c.253C>T	p.Arg85Trp	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.190C>T	p.Arg64Trp	missense	Exon 5 of 11	ENSP00000394354.2	Q11206-1
	ST3GAL4	ENST00000392669.6	TSL:1	c.190C>T	p.Arg64Trp	missense	Exon 5 of 11	ENSP00000376437.2	Q11206-1
	ST3GAL4	ENST00000526727.5	TSL:1	c.190C>T	p.Arg64Trp	missense	Exon 4 of 10	ENSP00000436047.1	Q11206-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251450 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.61		Loss of disorder (P = 0.036)
MVP		0.73
MPC		1.4
ClinPred		0.90	D
GERP RS		4.0
PromoterAI		-0.026	Neutral
Varity_R		0.26
gMVP		0.62
Mutation Taster		=66/34	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: rs765929837; hg19: chr11-126277154;