Variant rs139912060 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_173474.4(NTAN1):c.326T>G(p.Ile109Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NTAN1
NM_173474.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.17

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]

NTAN1 links:

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]

PDXDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTAN1	NM_173474.4 link	c.326T>G	p.Ile109Arg	missense_variant	Exon 4 of 10	ENST00000287706.8	NP_775745.1	Q96AB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTAN1	ENST00000287706.8 link	c.326T>G	p.Ile109Arg	missense_variant	Exon 4 of 10	1	NM_173474.4	ENSP00000287706.3		Q96AB6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251490

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461086

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726936

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;.;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

T;.;D;D;T

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.83

D;D;D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.2

D;.;.;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

D;.;.;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;.

Polyphen

0.88

P;.;.;.;.

Vest4

0.77

MutPred

0.72

Gain of sheet (P = 0.0101);.;.;.;.;

MVP

0.68

MPC

0.54

ClinPred

0.99

GERP RS

5.4

Varity_R

0.91

gMVP

0.93

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over