NM_173474.4:c.638C>T

Variant summary

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

The NM_173474.4(NTAN1):​c.638C>T​(p.Pro213Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NTAN1
NM_173474.4 missense, splice_region

Scores

7
12
Splicing: ADA: 0.4336
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40
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]

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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=0.22614256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTAN1NM_173474.4 linkc.638C>T p.Pro213Leu missense_variant, splice_region_variant Exon 8 of 10 ENST00000287706.8 NP_775745.1 Q96AB6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTAN1ENST00000287706.8 linkc.638C>T p.Pro213Leu missense_variant, splice_region_variant Exon 8 of 10 1 NM_173474.4 ENSP00000287706.3 Q96AB6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1408492
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
703796
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.092
T;.;.;.;.
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D;.;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.23
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;.;.;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.1
D;.;.;D;D
REVEL
Benign
0.049
Sift
Benign
0.18
T;.;.;T;T
Sift4G
Benign
0.17
T;T;T;T;.
Polyphen
0.23
B;.;.;.;.
Vest4
0.59
MutPred
0.29
Gain of catalytic residue at P213 (P = 0.015);.;.;.;.;
MVP
0.59
MPC
0.23
ClinPred
0.88
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.22
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.43
dbscSNV1_RF
Benign
0.33
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: rs777400530; hg19: chr16-15133827; API