9-85588358-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001330701.2(AGTPBP1):c.2843G>A(p.Arg948Gln) variant causes a missense change. 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: 6.08

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 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, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTPBP1	NM_001330701.2	c.2843G>A	p.Arg948Gln	missense_variant	21/26	ENST00000357081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.2843G>A	p.Arg948Gln	missense_variant	21/26	5	NM_001330701.2	P1
AGTPBP1	ENST00000376083.7	c.2723G>A	p.Arg908Gln	missense_variant	21/26	1
AGTPBP1	ENST00000337006.8	c.2999G>A	p.Arg1000Gln	missense_variant	20/25	5
AGTPBP1	ENST00000628899.1	c.2879G>A	p.Arg960Gln	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

Baylor Genetics

Jun 03, 2020

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
Cadd	Pathogenic	30
Dann	Pathogenic	1.0
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.6	D;.;D;.
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;.;D;.
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.94
MutPred		0.68		.;.;Loss of sheet (P = 0.1158);.;
MVP		0.55
MPC		1.8
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.77
gMVP		0.93

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: rs1828746127; hg19: chr9-88203273;