3-187051321-C-G

Variant names:

• chr3-187051321-C-G
• rs760546808
• NM_173216.2:c.680C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173216.2(ST6GAL1):​c.680C>G​(p.Thr227Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T227N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GAL1 NM_173216.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.37
• Publications: 0 publications found

Genes affected

ST6GAL1 (HGNC:10860): (ST6 beta-galactoside alpha-2,6-sialyltransferase 1) This gene encodes a member of glycosyltransferase family 29. The encoded protein is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The protein, which is normally found in the Golgi but can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CD75, and CD76. This gene has been incorrectly referred to as CD75. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL1	NM_173216.2	c.680C>G	p.Thr227Ser	missense_variant	Exon 5 of 8	ENST00000169298.8	NP_775323.1
ST6GAL1	NM_001353916.2	c.680C>G	p.Thr227Ser	missense_variant	Exon 3 of 6		NP_001340845.1
ST6GAL1	NM_003032.3	c.680C>G	p.Thr227Ser	missense_variant	Exon 4 of 7		NP_003023.1
ST6GAL1	NM_173217.2	c.-14C>G		5_prime_UTR_variant	Exon 4 of 7		NP_775324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.680C>G	p.Thr227Ser	missense_variant	Exon 5 of 8	1	NM_173216.2	ENSP00000169298.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		5.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		1.0	D;D
Vest4		0.86
MutPred		0.87		Gain of ubiquitination at K226 (P = 0.0872);Gain of ubiquitination at K226 (P = 0.0872);
MVP		0.42
MPC		0.52
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.81
Mutation Taster		=81/19	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: rs760546808; hg19: chr3-186769109;