18-46680461-C-A

Variant summary

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

The NM_013305.6(ST8SIA5):​c.712G>T​(p.Val238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ST8SIA5
NM_013305.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59
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]

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=0.102504075).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ST8SIA5NM_013305.6 linkuse as main transcriptc.712G>T p.Val238Leu missense_variant 7/7 ENST00000315087.12 NP_037437.2
ST8SIA5NM_001307986.2 linkuse as main transcriptc.820G>T p.Val274Leu missense_variant 8/8 NP_001294915.1
ST8SIA5NM_001307987.2 linkuse as main transcriptc.619G>T p.Val207Leu missense_variant 6/6 NP_001294916.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ST8SIA5ENST00000315087.12 linkuse as main transcriptc.712G>T p.Val238Leu missense_variant 7/71 NM_013305.6 ENSP00000321343 P4O15466-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000421
AC:
1
AN:
237272
Hom.:
0
AF XY:
0.00000775
AC XY:
1
AN XY:
128978
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000944
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454992
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
723348
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000226
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsAug 01, 2022The c.712G>T (p.V238L) alteration is located in exon 7 (coding exon 7) of the ST8SIA5 gene. This alteration results from a G to T substitution at nucleotide position 712, causing the valine (V) at amino acid position 238 to be replaced by a leucine (L). 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
0.13
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
19
DANN
Benign
0.91
DEOGEN2
Benign
0.018
.;T;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
.;L;.
MutationTaster
Benign
0.99
N;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.72
N;N;N
REVEL
Benign
0.070
Sift
Benign
0.32
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.0010, 0.0
.;B;B
Vest4
0.032
MutPred
0.57
Loss of sheet (P = 0.0457);.;.;
MVP
0.26
MPC
0.52
ClinPred
0.055
T
GERP RS
2.3
Varity_R
0.056
gMVP
0.60

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.

Other links and lift over

dbSNP: rs1295767347; hg19: chr18-44260424; API