3-187075579-A-G

Variant names:

• chr3-187075579-A-G
• NM_173216.2:c.997A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173216.2(ST6GAL1):​c.997A>G​(p.Thr333Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GAL1 NM_173216.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19420394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL1	NM_173216.2	c.997A>G	p.Thr333Ala	missense_variant	Exon 8 of 8	ENST00000169298.8	NP_775323.1
ST6GAL1	NM_001353916.2	c.997A>G	p.Thr333Ala	missense_variant	Exon 6 of 6		NP_001340845.1
ST6GAL1	NM_003032.3	c.997A>G	p.Thr333Ala	missense_variant	Exon 7 of 7		NP_003023.1
ST6GAL1	NM_173217.2	c.304A>G	p.Thr102Ala	missense_variant	Exon 7 of 7		NP_775324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8	c.997A>G	p.Thr333Ala	missense_variant	Exon 8 of 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

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.997A>G (p.T333A) alteration is located in exon 8 (coding exon 5) of the ST6GAL1 gene. This alteration results from a A to G substitution at nucleotide position 997, causing the threonine (T) at amino acid position 333 to be replaced by an alanine (A). 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	Benign	0.091
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T;.;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.70	.;T;T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;.;N;.
PhyloP100		3.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.59	N;N;N;N
REVEL	Benign	0.051
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.015	B;.;B;.
Vest4		0.12
MutPred		0.59		Gain of catalytic residue at T333 (P = 0.1531);.;Gain of catalytic residue at T333 (P = 0.1531);.;
MVP		0.12
MPC		0.20
ClinPred		0.56	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.45
Mutation Taster		=53/47	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

hg19: chr3-186793367;