NM_001330701.2:c.3385A>G

Variant names:

• chr9-85575433-T-C
• rs60986482
• NM_001330701.2:c.3385A>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The NM_001330701.2(AGTPBP1):​c.3385A>G​(p.Lys1129Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000297 in 1,608,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: AGTPBP1 NM_001330701.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.82

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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.010993838).
• BP6: Variant 9-85575433-T-C is Benign according to our data. Variant chr9-85575433-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00175 (266/152250) while in subpopulation AFR AF= 0.00619 (257/41550). AF 95% confidence interval is 0.00556. There are 0 homozygotes in gnomad4. There are 131 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2	c.3385A>G	p.Lys1129Glu	missense_variant	Exon 25 of 26	ENST00000357081.8	NP_001317630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.3385A>G	p.Lys1129Glu	missense_variant	Exon 25 of 26	5	NM_001330701.2	ENSP00000349592.3

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 263 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000377 AC: 93 AN: 246710 Hom.: 0 AF XY: 0.000300 AC XY: 40 AN XY: 133526

Gnomad AFR exome AF: 0.00521

Gnomad AMR exome AF: 0.000152

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000146 AC: 212 AN: 1456528 Hom.: 0 Cov.: 30 AF XY: 0.000124 AC XY: 90 AN XY: 724562

Gnomad4 AFR exome AF: 0.00565

Gnomad4 AMR exome AF: 0.000139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000249

GnomAD4 genome AF: 0.00175 AC: 266 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74438

Gnomad4 AFR AF: 0.00619

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000582 Hom.: 2

Bravo AF: 0.00195

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000502 AC: 61

Asia WGS AF: 0.000578 AC: 3 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

AGTPBP1-related disorder Benign:1

Aug 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Inborn genetic diseases Benign:1

Nov 13, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;T;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;.;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.0	N;.;N;.
REVEL	Benign	0.14
Sift	Benign	0.21	T;.;T;.
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.13	B;.;P;B
Vest4		0.61
MVP		0.39
MPC		0.095
ClinPred		0.020	T
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs60986482; hg19: chr9-88190348;