9-85586895-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001330701.2(AGTPBP1):c.2969A>T(p.His990Leu) variant causes a missense 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGTPBP1 NM_001330701.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802
• PP5: Variant 9-85586895-T-A is Pathogenic according to our data. Variant chr9-85586895-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 599367.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTPBP1	NM_001330701.2	c.2969A>T	p.His990Leu	missense_variant	22/26	ENST00000357081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.2969A>T	p.His990Leu	missense_variant	22/26	5	NM_001330701.2	P1
AGTPBP1	ENST00000376083.7	c.2849A>T	p.His950Leu	missense_variant	22/26	1
AGTPBP1	ENST00000337006.8	c.3125A>T	p.His1042Leu	missense_variant	21/25	5
AGTPBP1	ENST00000628899.1	c.3005A>T	p.His1002Leu	missense_variant	21/25	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodegeneration, childhood-onset, with cerebellar atrophy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 11, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
Cadd	Pathogenic	27
Dann	Uncertain	0.98
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-7.2	D;.;D;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.014	D;.;D;.
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		0.97	D;.;D;P
Vest4		0.90
MutPred		0.61		.;.;Loss of disorder (P = 0.0362);.;
MVP		0.44
MPC		1.5
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.75
gMVP		0.89

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

Other links and lift over

dbSNP: rs1564034077; hg19: chr9-88201810;