Variant 18-46680173-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013305.6(ST8SIA5):c.1000A>C(p.Thr334Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ST8SIA5
NM_013305.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19

Variant links:

Genes affected

ST8SIA5 (HGNC:17827): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 5) The protein encoded by this gene is a type II membrane protein that may be present in the Golgi apparatus. The encoded protein, which is a member of glycosyltransferase family 29, may be involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, and GT3 from GD1a, GT1b, GM1b, and GD3, respectively. [provided by RefSeq, Jul 2008]

ST8SIA5 links:

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=0.14741966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ST8SIA5	NM_013305.6 linkuse as main transcript	c.1000A>C	p.Thr334Pro	missense_variant	7/7	ENST00000315087.12	NP_037437.2
ST8SIA5	NM_001307986.2 linkuse as main transcript	c.1108A>C	p.Thr370Pro	missense_variant	8/8		NP_001294915.1
ST8SIA5	NM_001307987.2 linkuse as main transcript	c.907A>C	p.Thr303Pro	missense_variant	6/6		NP_001294916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA5	ENST00000315087.12 linkuse as main transcript	c.1000A>C	p.Thr334Pro	missense_variant	7/7	1	NM_013305.6	ENSP00000321343	P4	O15466-1
ST8SIA5	ENST00000538168.5 linkuse as main transcript	c.1108A>C	p.Thr370Pro	missense_variant	8/8	2		ENSP00000445492	A1	O15466-2
ST8SIA5	ENST00000536490.1 linkuse as main transcript	c.907A>C	p.Thr303Pro	missense_variant	6/6	2		ENSP00000443683
ST8SIA5	ENST00000590497.5 linkuse as main transcript	n.1164A>C		non_coding_transcript_exon_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000437

AC:

AN:

251454

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000178

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.000532

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.0000412

AC:

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 06, 2024

The c.1000A>C (p.T334P) alteration is located in exon 7 (coding exon 7) of the ST8SIA5 gene. This alteration results from a A to C substitution at nucleotide position 1000, causing the threonine (T) at amino acid position 334 to be replaced by a proline (P). 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

0.26

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

.;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.15

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.19

T;T;D

Sift4G

Benign

0.23

T;T;T

Polyphen

1.0, 0.98

.;D;D

Vest4

0.51

MVP

0.44

MPC

0.92

ClinPred

0.17

GERP RS

3.0

Varity_R

0.56

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over