chr8-133464796-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173344.3(ST3GAL1):c.665C>T(p.Thr222Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,272 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ST3GAL1
NM_173344.3 missense
NM_173344.3 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 9.86
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]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
ST3GAL1 | NM_173344.3 | c.665C>T | p.Thr222Ile | missense_variant | 7/10 | ENST00000522652.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST3GAL1 | ENST00000522652.6 | c.665C>T | p.Thr222Ile | missense_variant | 7/10 | 1 | NM_173344.3 | P1 | |
ST3GAL1 | ENST00000521180.5 | c.665C>T | p.Thr222Ile | missense_variant | 6/9 | 1 | P1 | ||
ST3GAL1 | ENST00000648219.1 | c.665C>T | p.Thr222Ile | missense_variant | 9/12 | P1 | |||
ST3GAL1 | ENST00000523854.5 | c.275C>T | p.Thr92Ile | missense_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250186Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135214
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461272Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726940
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2023 | The c.665C>T (p.T222I) alteration is located in exon 6 (coding exon 3) of the ST3GAL1 gene. This alteration results from a C to T substitution at nucleotide position 665, causing the threonine (T) at amino acid position 222 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D
Sift4G
Uncertain
D;D;.;D;.
Polyphen
D;D;D;D;.
Vest4
MutPred
Loss of glycosylation at T222 (P = 0.0615);Loss of glycosylation at T222 (P = 0.0615);Loss of glycosylation at T222 (P = 0.0615);Loss of glycosylation at T222 (P = 0.0615);.;
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at