9-85547120-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330701.2(AGTPBP1):c.3670T>G(p.Tyr1224Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AGTPBP1 NM_001330701.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079623014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTPBP1	NM_001330701.2	c.3670T>G	p.Tyr1224Asp	missense_variant	26/26	ENST00000357081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.3670T>G	p.Tyr1224Asp	missense_variant	26/26	5	NM_001330701.2	P1
AGTPBP1	ENST00000376083.7	c.3550T>G	p.Tyr1184Asp	missense_variant	26/26	1
AGTPBP1	ENST00000337006.8	c.3826T>G	p.Tyr1276Asp	missense_variant	25/25	5
AGTPBP1	ENST00000628899.1	c.3706T>G	p.Tyr1236Asp	missense_variant	25/25	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456772 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724830

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.3550T>G (p.Y1184D) alteration is located in exon 26 (coding exon 25) of the AGTPBP1 gene. This alteration results from a T to G substitution at nucleotide position 3550, causing the tyrosine (Y) at amino acid position 1184 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	17
Dann	Benign	0.97
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.080	N;.;N;.
REVEL	Benign	0.065
Sift	Benign	0.050	D;.;D;.
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.062	B;.;B;B
Vest4		0.26
MutPred		0.12		.;.;Gain of relative solvent accessibility (P = 0.0249);.;
MVP		0.22
MPC		0.092
ClinPred		0.12	T
GERP RS		3.7
Varity_R		0.057
gMVP		0.16

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: chr9-88162035;