10-17321067-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004470.3(ST8SIA6):ā€‹c.1008A>Cā€‹(p.Lys336Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ST8SIA6
NM_001004470.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.462
Variant links:
Genes affected
ST8SIA6 (HGNC:23317): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 6) This gene encodes a member of the glycosyltransferase 29 protein family. Members of this protein family synthesize sialylglycoconjugates. Sialylation may contribute to multidrug resistance in cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.09274009).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ST8SIA6NM_001004470.3 linkuse as main transcriptc.1008A>C p.Lys336Asn missense_variant 8/8 ENST00000377602.5 NP_001004470.1 P61647

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ST8SIA6ENST00000377602.5 linkuse as main transcriptc.1008A>C p.Lys336Asn missense_variant 8/81 NM_001004470.3 ENSP00000366827.4 P61647
ST8SIA6ENST00000440449.5 linkuse as main transcriptc.345+123A>C intron_variant 5 ENSP00000388343.1 H0Y405
ST8SIA6ENST00000648997.1 linkuse as main transcriptn.*750A>C non_coding_transcript_exon_variant 9/9 ENSP00000497856.1 A0A3B3ITM3
ST8SIA6ENST00000648997.1 linkuse as main transcriptn.*750A>C 3_prime_UTR_variant 9/9 ENSP00000497856.1 A0A3B3ITM3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingAmbry GeneticsNov 08, 2022The c.1008A>C (p.K336N) alteration is located in exon 8 (coding exon 8) of the ST8SIA6 gene. This alteration results from a A to C substitution at nucleotide position 1008, causing the lysine (K) at amino acid position 336 to be replaced by an asparagine (N). 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
0.15
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0094
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.099
N
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.093
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.47
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.73
N
REVEL
Benign
0.035
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.019
D
Polyphen
0.081
B
Vest4
0.15
MutPred
0.56
Loss of methylation at K336 (P = 0.0056);
MVP
0.31
MPC
0.057
ClinPred
0.28
T
GERP RS
-2.5
Varity_R
0.18
gMVP
0.30

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: chr10-17363066; API