11-126406962-G-C

Variant names:

• chr11-126406962-G-C
• rs201196480
• NM_001254757.2:c.121G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001254757.2(ST3GAL4):​c.121G>C​(p.Glu41Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. E41K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST3GAL4 NM_001254757.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.121G>C	p.Glu41Gln	missense	Exon 4 of 11	NP_001241686.1	Q11206-1
	ST3GAL4	NM_001348396.2		c.184G>C	p.Glu62Gln	missense	Exon 5 of 12	NP_001335325.1	A0A7P0RGI5
	ST3GAL4	NM_001348397.2		c.184G>C	p.Glu62Gln	missense	Exon 5 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.121G>C	p.Glu41Gln	missense	Exon 4 of 11	ENSP00000394354.2	Q11206-1
	ST3GAL4	ENST00000392669.6	TSL:1	c.121G>C	p.Glu41Gln	missense	Exon 4 of 11	ENSP00000376437.2	Q11206-1
	ST3GAL4	ENST00000526727.5	TSL:1	c.121G>C	p.Glu41Gln	missense	Exon 3 of 10	ENSP00000436047.1	Q11206-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Pathogenic	33
DANN	Uncertain	0.97
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.0062
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.066
Sift	Benign	0.067	T
Sift4G	Benign	0.56	T
Polyphen		0.17	B
Vest4		0.26
MutPred		0.34		Loss of glycosylation at P40 (P = 0.0753)
MVP		0.46
MPC		0.63
ClinPred		0.27	T
GERP RS		3.2
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.46
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.93		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.93		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201196480; hg19: chr11-126276857;