9-85588463-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001330701.2(AGTPBP1):c.2738T>A(p.Val913Asp) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGTPBP1 NM_001330701.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.08

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTPBP1	NM_001330701.2	c.2738T>A	p.Val913Asp	missense_variant	21/26	ENST00000357081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.2738T>A	p.Val913Asp	missense_variant	21/26	5	NM_001330701.2	P1
AGTPBP1	ENST00000376083.7	c.2618T>A	p.Val873Asp	missense_variant	21/26	1
AGTPBP1	ENST00000337006.8	c.2894T>A	p.Val965Asp	missense_variant	20/25	5
AGTPBP1	ENST00000628899.1	c.2774T>A	p.Val925Asp	missense_variant	20/25	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
Cadd	Pathogenic	29
Dann	Uncertain	0.98
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.94	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.5	D;.;D;.
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D;.;D;.
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.49	P;.;B;P
Vest4		0.77
MutPred		0.86		.;.;Loss of stability (P = 0.0443);.;
MVP		0.45
MPC		1.5
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.74
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-88203378;