rs757247613

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_013305.6(ST8SIA5):​c.556G>T​(p.Asp186Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D186N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ST8SIA5
NM_013305.6 missense

Scores

11
7
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45
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]

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ACMG classification

Classification made for transcript

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, 0.969

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST8SIA5NM_013305.6 linkc.556G>T p.Asp186Tyr missense_variant Exon 5 of 7 ENST00000315087.12 NP_037437.2 O15466-1
ST8SIA5NM_001307986.2 linkc.664G>T p.Asp222Tyr missense_variant Exon 6 of 8 NP_001294915.1 O15466-2
ST8SIA5NM_001307987.2 linkc.463G>T p.Asp155Tyr missense_variant Exon 4 of 6 NP_001294916.1 O15466F5H8D1B7Z5F7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ST8SIA5ENST00000315087.12 linkc.556G>T p.Asp186Tyr missense_variant Exon 5 of 7 1 NM_013305.6 ENSP00000321343.6 O15466-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727234
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
.;T;T
Eigen
Pathogenic
0.97
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Pathogenic
3.8
.;H;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-6.9
D;D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.98
MutPred
0.84
Loss of stability (P = 0.102);.;.;
MVP
0.86
MPC
1.6
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.90
gMVP
0.92

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: chr18-44266150; API