16-15047873-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001270766.2(NTAN1):​c.-84G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NTAN1
NM_001270766.2 5_prime_UTR_premature_start_codon_gain

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTAN1NM_173474.4 linkc.232G>A p.Val78Met missense_variant Exon 3 of 10 ENST00000287706.8 NP_775745.1 Q96AB6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTAN1ENST00000287706.8 linkc.232G>A p.Val78Met missense_variant Exon 3 of 10 1 NM_173474.4 ENSP00000287706.3 Q96AB6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.232G>A (p.V78M) alteration is located in exon 3 (coding exon 3) of the NTAN1 gene. This alteration results from a G to A substitution at nucleotide position 232, causing the valine (V) at amino acid position 78 to be replaced by a methionine (M). 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.43
T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.8
M;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.28
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0050
D;.
Polyphen
0.93
P;.
Vest4
0.64
MutPred
0.49
Loss of sheet (P = 0.0357);.;
MVP
0.56
MPC
0.50
ClinPred
0.96
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-15141730; API