8-133464866-C-T

Position:

• chr8-133464866-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173344.3(ST3GAL1):​c.595G>A​(p.Gly199Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: ST3GAL1 NM_173344.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.853

Genes affected

ST3GAL1 (HGNC:10862): (ST3 beta-galactoside alpha-2,3-sialyltransferase 1) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi but can be proteolytically processed to a soluble form. Correct glycosylation of the encoded protein may be critical to its sialyltransferase activity. This protein, which is a member of glycosyltransferase family 29, can use the same acceptor substrates as does sialyltransferase 4B. Two transcript variants encoding the same protein have been found for this gene. Other transcript variants may exist, but have not been fully characterized yet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21514544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST3GAL1	NM_173344.3	c.595G>A	p.Gly199Arg	missense_variant	7/10	ENST00000522652.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST3GAL1	ENST00000522652.6	c.595G>A	p.Gly199Arg	missense_variant	7/10	1	NM_173344.3	P1
ST3GAL1	ENST00000521180.5	c.595G>A	p.Gly199Arg	missense_variant	6/9	1		P1
ST3GAL1	ENST00000648219.1	c.595G>A	p.Gly199Arg	missense_variant	9/12			P1
ST3GAL1	ENST00000523854.5	c.205G>A	p.Gly69Arg	missense_variant	3/3	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

Nov 29, 2023

The c.595G>A (p.G199R) alteration is located in exon 6 (coding exon 3) of the ST3GAL1 gene. This alteration results from a G to A substitution at nucleotide position 595, causing the glycine (G) at amino acid position 199 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.096	T;T;T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.38	T;.;.;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L;L;.
MutationTaster	Benign	0.53	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N;N;.;N;N
REVEL	Benign	0.050
Sift	Benign	0.50	T;T;.;T;T
Sift4G	Benign	0.58	T;T;.;T;.
Polyphen		0.0060	B;B;B;B;.
Vest4		0.21
MutPred		0.58		Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);.;
MVP		0.082
ClinPred		0.83	D
GERP RS		4.9
Varity_R		0.13
gMVP		0.71

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: chr8-134477109;