Variant 9-85586956-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate

The NM_001330701.2(AGTPBP1):c.2908C>T(p.Arg970Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AGTPBP1
NM_001330701.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.59

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a active_site Nucleophile (size 0) in uniprot entity CBPC1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2 linkuse as main transcript	c.2908C>T	p.Arg970Cys	missense_variant	22/26	ENST00000357081.8	NP_001317630.1	Q9UPW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AGTPBP1	ENST00000357081.8 linkuse as main transcript	c.2908C>T	p.Arg970Cys	missense_variant	22/26	5	NM_001330701.2	ENSP00000349592.3	Q9UPW5-1
AGTPBP1	ENST00000376083.7 linkuse as main transcript	c.2788C>T	p.Arg930Cys	missense_variant	22/26	1		ENSP00000365251.3	Q9UPW5-2
AGTPBP1	ENST00000337006.8 linkuse as main transcript	c.3064C>T	p.Arg1022Cys	missense_variant	21/25	5		ENSP00000338512.5	J3KNS1
AGTPBP1	ENST00000628899.1 linkuse as main transcript	c.2944C>T	p.Arg982Cys	missense_variant	21/25	2		ENSP00000487074.1	Q9UPW5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727010

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2023

The c.2788C>T (p.R930C) alteration is located in exon 22 (coding exon 21) of the AGTPBP1 gene. This alteration results from a C to T substitution at nucleotide position 2788, causing the arginine (R) at amino acid position 930 to be replaced by a cysteine (C). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

.;.;T;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Pathogenic

0.93

D;D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

4.3

.;.;H;.

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-7.1

D;.;D;.

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

D;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.97

MutPred

0.79

.;.;Gain of catalytic residue at S972 (P = 0.0286);.;

MVP

0.72

MPC

2.0

ClinPred

1.0

GERP RS

5.7

Varity_R

0.83

gMVP

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.31

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.31

Position offset: 4

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over