dbSNP rs771215054: ST6GAL1:p.Asp157Asn (chr3-187043172-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_173216.2(ST6GAL1):c.469G>A(p.Asp157Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D157H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ST6GAL1
NM_173216.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.91

Publications

0 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]

ST6GAL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL1	NM_173216.2 link	c.469G>A	p.Asp157Asn	missense_variant	Exon 4 of 8	ENST00000169298.8	NP_775323.1	P15907-1
ST6GAL1	NM_001353916.2 link	c.469G>A	p.Asp157Asn	missense_variant	Exon 2 of 6		NP_001340845.1
ST6GAL1	NM_003032.3 link	c.469G>A	p.Asp157Asn	missense_variant	Exon 3 of 7		NP_003023.1	P15907-1
ST6GAL1	NM_173217.2 link	c.-87+4299G>A		intron_variant	Intron 3 of 6		NP_775324.1	P15907-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL1	ENST00000169298.8 link	c.469G>A	p.Asp157Asn	missense_variant	Exon 4 of 8	1	NM_173216.2	ENSP00000169298.3		P15907-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251170

AF XY:

0.0000221

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

6.9

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;D

Vest4

0.51

MutPred

0.56

Gain of catalytic residue at D157 (P = 0.0032);Gain of catalytic residue at D157 (P = 0.0032);

MVP

0.38

MPC

0.54

ClinPred

0.82

GERP RS

5.6

Varity_R

0.29

gMVP

0.53

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs771215054

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over