Genetic Variant NM_001330701.2:c.3659T>C (chr9-85547131-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001330701.2(AGTPBP1):c.3659T>C(p.Leu1220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,624 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: 0.0000014 ( 0 hom. )

Consequence

AGTPBP1
NM_001330701.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.395

Variant links:

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]

AGTPBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013980776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2 link	c.3659T>C	p.Leu1220Ser	missense_variant	Exon 26 of 26	ENST00000357081.8	NP_001317630.1	Q9UPW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGTPBP1	ENST00000357081.8 link	c.3659T>C	p.Leu1220Ser	missense_variant	Exon 26 of 26	5	NM_001330701.2	ENSP00000349592.3	Q9UPW5-1
AGTPBP1	ENST00000376083.7 link	c.3539T>C	p.Leu1180Ser	missense_variant	Exon 26 of 26	1		ENSP00000365251.3	Q9UPW5-2
AGTPBP1	ENST00000337006.8 link	c.3815T>C	p.Leu1272Ser	missense_variant	Exon 25 of 25	5		ENSP00000338512.5	J3KNS1
AGTPBP1	ENST00000628899.1 link	c.3695T>C	p.Leu1232Ser	missense_variant	Exon 25 of 25	2		ENSP00000487074.1	Q9UPW5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248802

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459624

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726204

show subpopulations

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:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3539T>C (p.L1180S) alteration is located in exon 26 (coding exon 25) of the AGTPBP1 gene. This alteration results from a T to C substitution at nucleotide position 3539, causing the leucine (L) at amino acid position 1180 to be replaced by a serine (S). 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

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.9

DANN

Benign

0.95

DEOGEN2

Benign

0.039

.;.;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.2

.;.;N;.

PrimateAI

Benign

0.31

PROVEAN

Benign

0.49

N;.;N;.

REVEL

Benign

0.018

Sift

Benign

0.20

T;.;T;.

Sift4G

Benign

0.71

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.072

MutPred

0.15

.;.;Gain of phosphorylation at L1220 (P = 0.0099);.;

MVP

0.099

MPC

0.070

ClinPred

0.026

GERP RS

0.58

Varity_R

0.028

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over