rs777284898

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173216.2(ST6GAL1):​c.614A>G​(p.His205Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ST6GAL1
NM_173216.2 missense

Scores

7
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

Publications

1 publications found
Variant links:
Genes affected
ST6GAL1 (HGNC:10860): (ST6 beta-galactoside alpha-2,6-sialyltransferase 1) This gene encodes a member of glycosyltransferase family 29. The encoded protein is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The protein, which is normally found in the Golgi but can be proteolytically processed to a soluble form, is involved in the generation of the cell-surface carbohydrate determinants and differentiation antigens HB-6, CD75, and CD76. This gene has been incorrectly referred to as CD75. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ST6GAL1NM_173216.2 linkc.614A>G p.His205Arg missense_variant Exon 5 of 8 ENST00000169298.8 NP_775323.1 P15907-1
ST6GAL1NM_001353916.2 linkc.614A>G p.His205Arg missense_variant Exon 3 of 6 NP_001340845.1
ST6GAL1NM_003032.3 linkc.614A>G p.His205Arg missense_variant Exon 4 of 7 NP_003023.1 P15907-1
ST6GAL1NM_173217.2 linkc.-80A>G 5_prime_UTR_variant Exon 4 of 7 NP_775324.1 P15907-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ST6GAL1ENST00000169298.8 linkc.614A>G p.His205Arg missense_variant Exon 5 of 8 1 NM_173216.2 ENSP00000169298.3 P15907-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000796
AC:
2
AN:
251344
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461806
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727208
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111940
Other (OTH)
AF:
0.00
AC:
0
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.614A>G (p.H205R) alteration is located in exon 5 (coding exon 2) of the ST6GAL1 gene. This alteration results from a A to G substitution at nucleotide position 614, causing the histidine (H) at amino acid position 205 to be replaced by an arginine (R). 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
Pathogenic
0.62
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
.;D
M_CAP
Benign
0.040
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.7
M;M
PhyloP100
6.3
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-7.1
D;D
REVEL
Uncertain
0.53
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.93
MutPred
0.72
Gain of disorder (P = 0.0765);Gain of disorder (P = 0.0765);
MVP
0.37
MPC
0.52
ClinPred
0.99
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.97
gMVP
0.96
Mutation Taster
=22/78
disease causing

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

Other links and lift over

dbSNP: rs777284898; hg19: chr3-186769043; API