Variant 9-85586961-C-CTACATG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_001330701.2(AGTPBP1):c.2904-7_2904-2dupCATGTA variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,588 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AGTPBP1
NM_001330701.2 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

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 Uncertain_significance. Variant got 4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.035044827 fraction of the gene. Cryptic splice site detected, with MaxEntScore 2.8, offset of 0 (no position change), new splice context is: ttatgtacatgtacatgtAGtca. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2 linkuse as main transcript	c.2904-7_2904-2dupCATGTA		splice_acceptor_variant, intron_variant		ENST00000357081.8	NP_001317630.1	Q9UPW5-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AGTPBP1	ENST00000357081.8 linkuse as main transcript	c.2904-2_2904-1insCATGTA	splice_acceptor_variant, intron_variant	5	NM_001330701.2	ENSP00000349592.3	Q9UPW5-1
AGTPBP1	ENST00000376083.7 linkuse as main transcript	c.2784-2_2784-1insCATGTA	splice_acceptor_variant, intron_variant	1		ENSP00000365251.3	Q9UPW5-2
AGTPBP1	ENST00000337006.8 linkuse as main transcript	c.3060-2_3060-1insCATGTA	splice_acceptor_variant, intron_variant	5		ENSP00000338512.5	J3KNS1
AGTPBP1	ENST00000628899.1 linkuse as main transcript	c.2940-2_2940-1insCATGTA	splice_acceptor_variant, intron_variant	2		ENSP00000487074.1	Q9UPW5-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461410

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726986

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodegeneration, childhood-onset, with cerebellar atrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genomics Laboratory, Washington University in St. Louis

Oct 07, 2024

The AGTPBP1 c.2904-7_2904-2dup variant, to our knowledge, has not been reported in the medical literature. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on AGTPBP1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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