16-15055920-C-T

Variant summary

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

The NM_173474.4(NTAN1):​c.52G>A​(p.Asp18Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,232,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NTAN1
NM_173474.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66
Variant links:
Genes affected
NTAN1 (HGNC:29909): (N-terminal asparagine amidase) The protein encoded by this gene functions in a step-wise process of protein degradation through the N-end rule pathway. This protein acts as a tertiary destabilizing enzyme that deamidates N-terminal L-Asn residues on proteins to produce N-terminal L-Asp. L-Asp substrates are subsequently conjugated to L-Arg, which is recognized by specific E3 ubiquitin ligases and targeted to the proteasome. Pseudogenes of this gene are located on the long arms of chromosomes 8, 10 and 12. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]
PDXDC1 (HGNC:28995): (pyridoxal dependent decarboxylase domain containing 1) Enables cadherin binding activity. Predicted to be involved in carboxylic acid metabolic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2032316).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTAN1NM_173474.4 linkc.52G>A p.Asp18Asn missense_variant Exon 1 of 10 ENST00000287706.8 NP_775745.1 Q96AB6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTAN1ENST00000287706.8 linkc.52G>A p.Asp18Asn missense_variant Exon 1 of 10 1 NM_173474.4 ENSP00000287706.3 Q96AB6

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151986
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000278
AC:
3
AN:
1080708
Hom.:
0
Cov.:
29
AF XY:
0.00000392
AC XY:
2
AN XY:
510836
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000217
Gnomad4 OTH exome
AF:
0.0000229
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151986
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.00
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
T;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.74
T;T
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.20
N;.
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-0.34
N;N
REVEL
Benign
0.063
Sift
Benign
0.27
T;D
Sift4G
Benign
0.33
T;.
Polyphen
0.078
B;.
Vest4
0.16
MutPred
0.14
Gain of MoRF binding (P = 0.0325);Gain of MoRF binding (P = 0.0325);
MVP
0.38
MPC
0.16
ClinPred
0.23
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.28
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs902106682; hg19: chr16-15149777; API