3-187075618-T-A

Position:

• chr3-187075618-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173216.2(ST6GAL1):​c.1036T>A​(p.Ser346Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GAL1 NM_173216.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96

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]

ST6GAL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GAL1	NM_173216.2	c.1036T>A	p.Ser346Thr	missense_variant	8/8	ENST00000169298.8	NP_775323.1
ST6GAL1	NM_001353916.2	c.1036T>A	p.Ser346Thr	missense_variant	6/6		NP_001340845.1
ST6GAL1	NM_003032.3	c.1036T>A	p.Ser346Thr	missense_variant	7/7		NP_003023.1
ST6GAL1	NM_173217.2	c.343T>A	p.Ser115Thr	missense_variant	7/7		NP_775324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.1036T>A	p.Ser346Thr	missense_variant	8/8	1	NM_173216.2	ENSP00000169298.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.1036T>A (p.S346T) alteration is located in exon 8 (coding exon 5) of the ST6GAL1 gene. This alteration results from a T to A substitution at nucleotide position 1036, causing the serine (S) at amino acid position 346 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.;T;T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	.;D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.7	M;.;M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.64
MutPred		0.48		Gain of phosphorylation at S346 (P = 0.0354);.;Gain of phosphorylation at S346 (P = 0.0354);.;
MVP		0.41
MPC		0.74
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.88

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-186793406;