rs193920832

Positions:

• chr10-17359547-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001345961.2(ST8SIA6):​c.-110G>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ST8SIA6 NM_001345961.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.14

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]

ST8SIA6 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA6	NM_001004470.3	c.344G>T	p.Trp115Leu	missense_variant	4/8	ENST00000377602.5	NP_001004470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA6	ENST00000377602.5	c.344G>T	p.Trp115Leu	missense_variant	4/8	1	NM_001004470.3	ENSP00000366827.4
ST8SIA6	ENST00000648997.1	n.*86G>T		non_coding_transcript_exon_variant	5/9			ENSP00000497856.1
ST8SIA6	ENST00000648997.1	n.*86G>T		3_prime_UTR_variant	5/9			ENSP00000497856.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.87		Loss of helix (P = 0.0558);
MVP		0.68
MPC		0.34
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.85
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs193920832; hg19: chr10-17401546; COSMIC: COSV66472229;