rs148724007

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001330701.2(AGTPBP1):c.3206G>T(p.Cys1069Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000383 in 1,610,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

AGTPBP1
NM_001330701.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.98

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

neurodegeneration, childhood-onset, with cerebellar atrophy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AGTPBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021485656).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000821 (125/152258) while in subpopulation AFR AF = 0.002 (83/41556). AF 95% confidence interval is 0.00165. There are 0 homozygotes in GnomAd4. There are 66 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330701.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGTPBP1	NM_001330701.2	MANE Select	c.3206G>T	p.Cys1069Phe	missense	Exon 24 of 26	NP_001317630.1	Q9UPW5-1
AGTPBP1	NM_001286715.1		c.3362G>T	p.Cys1121Phe	missense	Exon 23 of 25	NP_001273644.1	J3KNS1
AGTPBP1	NM_001286717.1		c.3242G>T	p.Cys1081Phe	missense	Exon 23 of 25	NP_001273646.1	Q9UPW5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGTPBP1	ENST00000357081.8	TSL:5 MANE Select	c.3206G>T	p.Cys1069Phe	missense	Exon 24 of 26	ENSP00000349592.3	Q9UPW5-1
AGTPBP1	ENST00000376083.7	TSL:1	c.3086G>T	p.Cys1029Phe	missense	Exon 24 of 26	ENSP00000365251.3	Q9UPW5-2
AGTPBP1	ENST00000337006.8	TSL:5	c.3362G>T	p.Cys1121Phe	missense	Exon 23 of 25	ENSP00000338512.5	J3KNS1

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000364

AC:

AN:

247282

AF XY:

0.000299

show subpopulations

Gnomad AFR exome

AF:

0.00151

Gnomad AMR exome

AF:

0.000686

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000338

Gnomad OTH exome

AF:

0.000668

GnomAD4 exome

AF:

0.000337

AC:

492

AN:

1458378

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

229

AN XY:

725506

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

33202

American (AMR)

AF:

0.000776

AC:

AN:

43822

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000283

AC:

314

AN:

1110836

Other (OTH)

AF:

0.000897

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152258

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41556

American (AMR)

AF:

0.00164

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68016

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000410

Hom.:

Bravo

AF:

0.000963

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000354

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodegeneration, childhood-onset, with cerebellar atrophy (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.010

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

4.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.3

REVEL

Benign

0.10

Sift

Uncertain

0.026

Sift4G

Uncertain

0.015

Polyphen

0.41

Vest4

0.58

MVP

0.33

MPC

1.6

ClinPred

0.041

GERP RS

4.6

Varity_R

0.36

gMVP

0.78

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over