NM_001330701.2:c.3349C>T

Variant names:

• chr9-85575469-G-A
• NM_001330701.2:c.3349C>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001330701.2(AGTPBP1):​c.3349C>T​(p.Gln1117*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGTPBP1 NM_001330701.2 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.22
• Publications: 0 publications found

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-85575469-G-A is Pathogenic according to our data. Variant chr9-85575469-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 3772519.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTPBP1	NM_001330701.2	MANE Select	c.3349C>T	p.Gln1117*	stop_gained	Exon 25 of 26	NP_001317630.1	Q9UPW5-1
	AGTPBP1	NM_001286715.1		c.3505C>T	p.Gln1169*	stop_gained	Exon 24 of 25	NP_001273644.1	J3KNS1
	AGTPBP1	NM_001286717.1		c.3385C>T	p.Gln1129*	stop_gained	Exon 24 of 25	NP_001273646.1	Q9UPW5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTPBP1	ENST00000357081.8	TSL:5 MANE Select	c.3349C>T	p.Gln1117*	stop_gained	Exon 25 of 26	ENSP00000349592.3	Q9UPW5-1
	AGTPBP1	ENST00000376083.7	TSL:1	c.3229C>T	p.Gln1077*	stop_gained	Exon 25 of 26	ENSP00000365251.3	Q9UPW5-2
	AGTPBP1	ENST00000337006.8	TSL:5	c.3505C>T	p.Gln1169*	stop_gained	Exon 24 of 25	ENSP00000338512.5	J3KNS1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448622 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720238

African (AFR) AF: 0.00 AC: 0 AN: 32898

American (AMR) AF: 0.00 AC: 0 AN: 41126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 38966

South Asian (SAS) AF: 0.00 AC: 0 AN: 82440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108506

Other (OTH) AF: 0.00 AC: 0 AN: 59882

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	49
DANN	Uncertain	1.0
Eigen	Pathogenic	1.3
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		9.2
Vest4		0.84
GERP RS		6.1
Mutation Taster		=6/194	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr9-88190384;