9-85547151-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001330701.2(AGTPBP1):c.3639A>C(p.Glu1213Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,613,038 control chromosomes in the GnomAD database, including 44 homozygotes. 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (44 hom.)
• Consequence: AGTPBP1 NM_001330701.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.311

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020323396).
• BP6: Variant 9-85547151-T-G is Benign according to our data. Variant chr9-85547151-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2659286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00414 (631/152328) while in subpopulation NFE AF= 0.0069 (469/68014). AF 95% confidence interval is 0.00638. There are 0 homozygotes in gnomad4. There are 282 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTPBP1	NM_001330701.2	c.3639A>C	p.Glu1213Asp	missense_variant	26/26	ENST00000357081.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.3639A>C	p.Glu1213Asp	missense_variant	26/26	5	NM_001330701.2	P1
AGTPBP1	ENST00000376083.7	c.3519A>C	p.Glu1173Asp	missense_variant	26/26	1
AGTPBP1	ENST00000337006.8	c.3795A>C	p.Glu1265Asp	missense_variant	25/25	5
AGTPBP1	ENST00000628899.1	c.3675A>C	p.Glu1225Asp	missense_variant	25/25	2

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 631 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00474 AC: 1185 AN: 249974 Hom.: 7 AF XY: 0.00506 AC XY: 684 AN XY: 135214

Gnomad AFR exome AF: 0.000742

Gnomad AMR exome AF: 0.00533

Gnomad ASJ exome AF: 0.00657

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00207

Gnomad FIN exome AF: 0.000741

Gnomad NFE exome AF: 0.00717

Gnomad OTH exome AF: 0.00575

GnomAD4 exome AF: 0.00570 AC: 8323 AN: 1460710 Hom.: 44 Cov.: 31 AF XY: 0.00563 AC XY: 4091 AN XY: 726740

Gnomad4 AFR exome AF: 0.000958

Gnomad4 AMR exome AF: 0.00531

Gnomad4 ASJ exome AF: 0.00678

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.000918

Gnomad4 NFE exome AF: 0.00644

Gnomad4 OTH exome AF: 0.00676

GnomAD4 genome AF: 0.00414 AC: 631 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74488

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00690

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00665 Hom.: 8

Bravo AF: 0.00465

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00698 AC: 60

ExAC AF: 0.00479 AC: 581

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00797

EpiControl AF: 0.00856

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

AGTPBP1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

AGTPBP1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	13
Dann	Benign	0.90
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.0020	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.74	D;D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.040	N;.;N;.
REVEL	Benign	0.031
Sift	Benign	0.58	T;.;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.086
MutPred		0.095		.;.;Loss of solvent accessibility (P = 0.0152);.;
MVP		0.21
MPC		0.050
ClinPred		0.0017	T
GERP RS		2.3
Varity_R		0.051
gMVP		0.068

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: rs138412470; hg19: chr9-88162066;