12-4720742-A-G

Variant summary

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

The NM_017417.2(GALNT8):ā€‹c.65A>Gā€‹(p.Asn22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000014 ( 1 hom. )

Consequence

GALNT8
NM_017417.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04
Variant links:
Genes affected
GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 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=0.12898314).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GALNT8NM_017417.2 linkc.65A>G p.Asn22Ser missense_variant Exon 1 of 11 ENST00000252318.7 NP_059113.1 Q9NY28

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GALNT8ENST00000252318.7 linkc.65A>G p.Asn22Ser missense_variant Exon 1 of 11 1 NM_017417.2 ENSP00000252318.2 Q9NY28
ENSG00000255639ENST00000648836.1 linkc.963+35417A>G intron_variant Intron 10 of 14 ENSP00000497305.1 A0A3B3ISG8
ENSG00000255639ENST00000543979.1 linkn.590-5790A>G intron_variant Intron 5 of 5 2
ENSG00000255639ENST00000544741.2 linkn.241-5790A>G intron_variant Intron 3 of 5 3 ENSP00000456318.2 H3BRM9

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251398
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461502
Hom.:
1
Cov.:
29
AF XY:
0.0000206
AC XY:
15
AN XY:
727100
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151
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
May 03, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.65A>G (p.N22S) alteration is located in exon 1 (coding exon 1) of the GALNT8 gene. This alteration results from a A to G substitution at nucleotide position 65, causing the asparagine (N) at amino acid position 22 to be replaced by a serine (S). 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
0.079
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0026
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
2.0
M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.12
Sift
Uncertain
0.019
D
Sift4G
Benign
0.066
T
Polyphen
0.90
P
Vest4
0.31
MutPred
0.26
Loss of sheet (P = 0.3635);
MVP
0.37
MPC
0.17
ClinPred
0.35
T
GERP RS
4.0
Varity_R
0.16
gMVP
0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747277653; hg19: chr12-4829908; API