rs760998543

Variant names:

• chr10-17390597-A-C
• rs760998543
• NM_001004470.3:c.224T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004470.3(ST8SIA6):​c.224T>G​(p.Leu75Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ST8SIA6 NM_001004470.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.632
• Publications: 0 publications found

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-AS1 (HGNC:44880): (ST8SIA6 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1498948).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004470.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA6	NM_001004470.3	MANE Select	c.224T>G	p.Leu75Arg	missense	Exon 3 of 8	NP_001004470.1	P61647
	ST8SIA6	NM_001345961.2		c.-299T>G		5_prime_UTR	Exon 3 of 9	NP_001332890.1
	ST8SIA6	NR_144322.2		n.564T>G		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA6	ENST00000377602.5	TSL:1 MANE Select	c.224T>G	p.Leu75Arg	missense	Exon 3 of 8	ENSP00000366827.4	P61647
	ST8SIA6-AS1	ENST00000457649.7	TSL:1	n.164+3522A>C		intron	N/A
	ST8SIA6	ENST00000648997.1		n.164T>G		non_coding_transcript_exon	Exon 3 of 9	ENSP00000497856.1	A0A3B3ITM3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251296 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461670 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111886

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.63
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.057
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.014	D
Polyphen		0.43	B
Vest4		0.50
MutPred		0.40		Gain of solvent accessibility (P = 0.0062)
MVP		0.20
MPC		0.061
ClinPred		0.12	T
GERP RS		-0.42
Varity_R		0.20
gMVP		0.31
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs760998543; hg19: chr10-17432596;