NM_001330701.2:c.3504-3465T>A

Variant names:

• chr9-85550751-A-T
• rs1030303
• NM_001330701.2:c.3504-3465T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330701.2(AGTPBP1):​c.3504-3465T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,934 control chromosomes in the GnomAD database, including 34,068 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34068 hom., cov: 31)
• Consequence: AGTPBP1 NM_001330701.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• neurodegeneration, childhood-onset, with cerebellar atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2	c.3504-3465T>A		intron_variant	Intron 25 of 25	ENST00000357081.8	NP_001317630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.3504-3465T>A		intron_variant	Intron 25 of 25	5	NM_001330701.2	ENSP00000349592.3
AGTPBP1	ENST00000376083.7	c.3384-3465T>A		intron_variant	Intron 25 of 25	1		ENSP00000365251.3
AGTPBP1	ENST00000337006.8	c.3660-3465T>A		intron_variant	Intron 24 of 24	5		ENSP00000338512.5
AGTPBP1	ENST00000628899.1	c.3540-3465T>A		intron_variant	Intron 24 of 24	2		ENSP00000487074.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99519 AN: 151816 Hom.: 34020 Cov.: 31

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99631 AN: 151934 Hom.: 34068 Cov.: 31 AF XY: 0.656 AC XY: 48681 AN XY: 74256

African (AFR) AF: 0.858 AC: 35599 AN: 41468

American (AMR) AF: 0.615 AC: 9388 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2296 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3314 AN: 5140

South Asian (SAS) AF: 0.730 AC: 3516 AN: 4816

European-Finnish (FIN) AF: 0.532 AC: 5621 AN: 10556

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37766 AN: 67922

Other (OTH) AF: 0.642 AC: 1347 AN: 2098

Alfa AF: 0.612 Hom.: 3683

Bravo AF: 0.668

Asia WGS AF: 0.661 AC: 2302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.38
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1030303; hg19: chr9-88165666;