chr9-127890749-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_013443.5(ST6GALNAC6):c.592C>T(p.Arg198Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
ST6GALNAC6
NM_013443.5 missense
NM_013443.5 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 4.07
Genes affected
ST6GALNAC6 (HGNC:23364): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 6) ST6GALNAC6 belongs to a family of sialyltransferases that modify proteins and ceramides on the cell surface to alter cell-cell or cell-extracellular matrix interactions (Tsuchida et al., 2003 [PubMed 12668675]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.745
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ST6GALNAC6 | NM_013443.5 | c.592C>T | p.Arg198Cys | missense_variant | 5/7 | ENST00000373146.6 | |
ST6GALNAC4-ST6GALNAC6-AK1 | NR_174625.1 | n.1468C>T | non_coding_transcript_exon_variant | 7/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ST6GALNAC6 | ENST00000373146.6 | c.592C>T | p.Arg198Cys | missense_variant | 5/7 | 1 | NM_013443.5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250518Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135484
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1460886Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 726578
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74362
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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 | May 24, 2023 | The c.592C>T (p.R198C) alteration is located in exon 5 (coding exon 4) of the ST6GALNAC6 gene. This alteration results from a C to T substitution at nucleotide position 592, causing the arginine (R) at amino acid position 198 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;.;D;.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;M;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;.;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;.
Polyphen
D;D;D;D;.;D;.
Vest4
MutPred
Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);.;.;Loss of MoRF binding (P = 5e-04);.;.;
MVP
MPC
1.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at