rs1030304

Variant names:

• chr9-85550834-A-G
• rs1030304
• NM_001330701.2:c.3504-3548T>C

Variant summary

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

The NM_001330701.2(AGTPBP1):​c.3504-3548T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 152,242 control chromosomes in the GnomAD database, including 13 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 0.0027 (13 hom., cov: 32)
• Consequence: AGTPBP1 NM_001330701.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 1 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330701.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTPBP1	NM_001330701.2	MANE Select	c.3504-3548T>C		intron	N/A	NP_001317630.1	Q9UPW5-1
	AGTPBP1	NM_001286715.1		c.3660-3548T>C		intron	N/A	NP_001273644.1	J3KNS1
	AGTPBP1	NM_001286717.1		c.3540-3548T>C		intron	N/A	NP_001273646.1	Q9UPW5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTPBP1	ENST00000357081.8	TSL:5 MANE Select	c.3504-3548T>C		intron	N/A	ENSP00000349592.3	Q9UPW5-1
	AGTPBP1	ENST00000376083.7	TSL:1	c.3384-3548T>C		intron	N/A	ENSP00000365251.3	Q9UPW5-2
	AGTPBP1	ENST00000337006.8	TSL:5	c.3660-3548T>C		intron	N/A	ENSP00000338512.5	J3KNS1

Frequencies

GnomAD3 genomes AF: 0.00267 AC: 406 AN: 152124 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00266 AC: 405 AN: 152242 Hom.: 13 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74458

African (AFR) AF: 0.0000722 AC: 3 AN: 41564

American (AMR) AF: 0.000915 AC: 14 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0711 AC: 368 AN: 5174

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00602 Hom.: 6

Bravo AF: 0.00348

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

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: rs1030304; hg19: chr9-88165749;