3-187043172-G-T

Variant names:

• chr3-187043172-G-T
• rs771215054
• NM_173216.2:c.469G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173216.2(ST6GAL1):​c.469G>T​(p.Asp157Tyr) 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. D157H) 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: 6.91
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL1	NM_173216.2	c.469G>T	p.Asp157Tyr	missense_variant	Exon 4 of 8	ENST00000169298.8	NP_775323.1
ST6GAL1	NM_001353916.2	c.469G>T	p.Asp157Tyr	missense_variant	Exon 2 of 6		NP_001340845.1
ST6GAL1	NM_003032.3	c.469G>T	p.Asp157Tyr	missense_variant	Exon 3 of 7		NP_003023.1
ST6GAL1	NM_173217.2	c.-87+4299G>T		intron_variant	Intron 3 of 6		NP_775324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.469G>T	p.Asp157Tyr	missense_variant	Exon 4 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.4	M;M
PhyloP100		6.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;D
Vest4		0.77
MutPred		0.56		Gain of phosphorylation at D157 (P = 0.0764);Gain of phosphorylation at D157 (P = 0.0764);
MVP		0.32
MPC		0.68
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.80
gMVP		0.76
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs771215054; hg19: chr3-186760960;