1-76313839-C-T

Variant summary

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

The NM_152996.4(ST6GALNAC3):​c.53C>T​(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ST6GALNAC3
NM_152996.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03
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]

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=0.07794458).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ST6GALNAC3NM_152996.4 linkc.53C>T p.Ala18Val missense_variant 2/5 ENST00000328299.4 NP_694541.2 Q8NDV1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ST6GALNAC3ENST00000328299.4 linkc.53C>T p.Ala18Val missense_variant 2/51 NM_152996.4 ENSP00000329214.3 Q8NDV1-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152002
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000435
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250888
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461334
Hom.:
0
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
726958
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152002
Hom.:
0
Cov.:
32
AF XY:
0.0000943
AC XY:
7
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.000435
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4

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 28, 2024The c.53C>T (p.A18V) alteration is located in exon 2 (coding exon 2) of the ST6GALNAC3 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a valine (V). 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
0.077
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.46
N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
0.050
N
REVEL
Benign
0.081
Sift
Benign
0.58
T
Sift4G
Benign
0.96
T
Polyphen
0.10
B
Vest4
0.36
MVP
0.061
MPC
0.064
ClinPred
0.070
T
GERP RS
4.3
Varity_R
0.031
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs372596931; hg19: chr1-76779524; COSMIC: COSV60320855; COSMIC: COSV60320855; API