chr3-138130923-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016161.3(A4GNT):​c.334G>A​(p.Asp112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

A4GNT
NM_016161.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.471
Variant links:
Genes affected
A4GNT (HGNC:17968): (alpha-1,4-N-acetylglucosaminyltransferase) This gene encodes a protein from the glycosyltransferase 32 family. The enzyme catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. It forms a unique glycan, GlcNAcalpha1-->4Galbeta-->R and is largely associated with the Golgi apparatus membrane. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038555324).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
A4GNTNM_016161.3 linkuse as main transcriptc.334G>A p.Asp112Asn missense_variant 2/3 ENST00000236709.4 NP_057245.1 Q9UNA3
A4GNTXM_017006543.3 linkuse as main transcriptc.334G>A p.Asp112Asn missense_variant 2/3 XP_016862032.1 Q9UNA3
A4GNTXM_017006544.2 linkuse as main transcriptc.334G>A p.Asp112Asn missense_variant 2/3 XP_016862033.1 Q9UNA3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
A4GNTENST00000236709.4 linkuse as main transcriptc.334G>A p.Asp112Asn missense_variant 2/31 NM_016161.3 ENSP00000236709.3 Q9UNA3

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000459
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000318
AC:
8
AN:
251462
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.0000150
AC:
22
AN:
1461886
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.0000654
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:
0.0000272
Hom.:
0
Bravo
AF:
0.000159
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

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 GeneticsJan 24, 2024The c.334G>A (p.D112N) alteration is located in exon 2 (coding exon 1) of the A4GNT gene. This alteration results from a G to A substitution at nucleotide position 334, causing the aspartic acid (D) at amino acid position 112 to be replaced by an asparagine (N). 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
0.083
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.0025
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.089
N
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.069
Sift
Benign
0.37
T
Sift4G
Benign
0.47
T
Polyphen
0.015
B
Vest4
0.064
MVP
0.18
MPC
0.11
ClinPred
0.021
T
GERP RS
2.4
Varity_R
0.038
gMVP
0.27

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: rs150885526; hg19: chr3-137849765; API