rs746058778

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_001330701.2(AGTPBP1):c.3590T>C(p.Ile1197Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AGTPBP1
NM_001330701.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

AGTPBP1 (HGNC:17258): (ATP/GTP binding carboxypeptidase 1) NNA1 is a zinc carboxypeptidase that contains nuclear localization signals and an ATP/GTP-binding motif that was initially cloned from regenerating spinal cord neurons of the mouse.[supplied by OMIM, Jul 2002]

AGTPBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030484319).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000328 (5/152234) while in subpopulation AMR AF= 0.000196 (3/15282). AF 95% confidence interval is 0.0000529. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2 link	c.3590T>C	p.Ile1197Thr	missense_variant	Exon 26 of 26	ENST00000357081.8	NP_001317630.1	Q9UPW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGTPBP1	ENST00000357081.8 link	c.3590T>C	p.Ile1197Thr	missense_variant	Exon 26 of 26	5	NM_001330701.2	ENSP00000349592.3	Q9UPW5-1
AGTPBP1	ENST00000376083.7 link	c.3470T>C	p.Ile1157Thr	missense_variant	Exon 26 of 26	1		ENSP00000365251.3	Q9UPW5-2
AGTPBP1	ENST00000337006.8 link	c.3746T>C	p.Ile1249Thr	missense_variant	Exon 25 of 25	5		ENSP00000338512.5	J3KNS1
AGTPBP1	ENST00000628899.1 link	c.3626T>C	p.Ile1209Thr	missense_variant	Exon 25 of 25	2		ENSP00000487074.1	Q9UPW5-3

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3470T>C (p.I1157T) alteration is located in exon 26 (coding exon 25) of the AGTPBP1 gene. This alteration results from a T to C substitution at nucleotide position 3470, causing the isoleucine (I) at amino acid position 1157 to be replaced by a threonine (T). 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

0.064

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.077

.;.;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.70

T;T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.030

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;.;N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

0.76

N;.;N;.

REVEL

Benign

0.049

Sift

Benign

0.59

T;.;T;.

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.0010

B;.;B;B

Vest4

0.12

MutPred

0.12

.;.;Gain of glycosylation at I1197 (P = 0.0182);.;

MVP

0.21

MPC

0.064

ClinPred

0.064

GERP RS

1.9

Varity_R

0.023

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over