3-98788134-A-G

Variant names:

• chr3-98788134-A-G
• NM_001323368.2:c.530A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001323368.2(ST3GAL6):​c.530A>G​(p.His177Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ST3GAL6 NM_001323368.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

Genes affected

ST3GAL6 (HGNC:18080): (ST3 beta-galactoside alpha-2,3-sialyltransferase 6) The protein encoded by this gene is a member of the sialyltransferase family. Members of this family are enzymes that transfer sialic acid from the activated cytidine 5'-monophospho-N-acetylneuraminic acid to terminal positions on sialylated glycolipids (gangliosides) or to the N- or O-linked sugar chains of glycoproteins. This protein has high specificity for neolactotetraosylceramide and neolactohexaosylceramide as glycolipid substrates and may contribute to the formation of selectin ligands and sialyl Lewis X, a carbohydrate important for cell-to-cell recognition and a blood group antigen. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3410977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323368.2. 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
	ST3GAL6	NM_001323368.2	MANE Select	c.530A>G	p.His177Arg	missense	Exon 7 of 10	NP_001310297.1	Q9Y274-1
	ST3GAL6	NM_001271145.2		c.689A>G	p.His230Arg	missense	Exon 7 of 10	NP_001258074.1	A0A087WXB8
	ST3GAL6	NM_001271146.2		c.530A>G	p.His177Arg	missense	Exon 7 of 10	NP_001258075.1	Q9Y274-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL6	ENST00000483910.6	TSL:1 MANE Select	c.530A>G	p.His177Arg	missense	Exon 7 of 10	ENSP00000417376.1	Q9Y274-1
	ST3GAL6	ENST00000394162.5	TSL:1	c.530A>G	p.His177Arg	missense	Exon 8 of 11	ENSP00000377717.1	Q9Y274-1
	ST3GAL6	ENST00000613264.5	TSL:1	c.530A>G	p.His177Arg	missense	Exon 7 of 10	ENSP00000480884.2	Q9Y274-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.057
Sift	Benign	0.096	T
Sift4G	Uncertain	0.026	D
Polyphen		0.052	B
Vest4		0.48
MutPred		0.49		Loss of glycosylation at T182 (P = 0.0286)
MVP		0.51
MPC		0.62
ClinPred		0.85	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.27
gMVP		0.47
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

hg19: chr3-98506978;