Genetic Variant ST6GALNAC3:p.Gly231Ser (chr1-76627519-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152996.4(ST6GALNAC3):c.691G>A(p.Gly231Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

ST6GALNAC3
NM_152996.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Publications

0 publications found

Variant links:

Genes affected

ST6GALNAC3 (HGNC:19343): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 3) ST6GALNAC3 belongs to a family of sialyltransferases that transfer sialic acids from CMP-sialic acid to terminal positions of carbohydrate groups in glycoproteins and glycolipids (Lee et al., 1999 [PubMed 10207017]).[supplied by OMIM, Mar 2008]

ST6GALNAC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03704405).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ST6GALNAC3	NM_152996.4	MANE Select	c.691G>A	p.Gly231Ser	missense	Exon 4 of 5	NP_694541.2	Q8NDV1-1
ST6GALNAC3	NM_001349111.2		c.727G>A	p.Gly243Ser	missense	Exon 5 of 6	NP_001336040.1
ST6GALNAC3	NM_001349108.2		c.496G>A	p.Gly166Ser	missense	Exon 3 of 4	NP_001336037.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC3	ENST00000328299.4	TSL:1 MANE Select	c.691G>A	p.Gly231Ser	missense	Exon 4 of 5	ENSP00000329214.3	Q8NDV1-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000442

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251116

AF XY:

0.0000147

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:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1460670

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1111126

Other (OTH)

AF:

0.0000166

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.0000329

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41368

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67904

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000264

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.71

M_CAP

Benign

0.0064

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.30

PhyloP100

1.7

PrimateAI

Benign

0.38

PROVEAN

Benign

0.59

REVEL

Benign

0.033

Sift

Benign

0.62

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.13

MutPred

0.46

Gain of phosphorylation at Y235 (P = 0.1145)

MVP

0.030

MPC

0.065

ClinPred

0.014

GERP RS

-3.3

Varity_R

0.044

gMVP

0.47

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over