NM_001330701.2:c.3504-5640C>A

Variant names:

• chr9-85552926-G-T
• rs10868320
• NM_001330701.2:c.3504-5640C>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.3504-5640C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,126 control chromosomes in the GnomAD database, including 8,939 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 0.28 (8939 hom., cov: 33)
• Consequence: AGTPBP1 NM_001330701.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTPBP1	NM_001330701.2	MANE Select	c.3504-5640C>A		intron	N/A	NP_001317630.1
	AGTPBP1	NM_001286715.1		c.3660-5640C>A		intron	N/A	NP_001273644.1
	AGTPBP1	NM_001286717.1		c.3540-5640C>A		intron	N/A	NP_001273646.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTPBP1	ENST00000357081.8	TSL:5 MANE Select	c.3504-5640C>A		intron	N/A	ENSP00000349592.3
	AGTPBP1	ENST00000376083.7	TSL:1	c.3384-5640C>A		intron	N/A	ENSP00000365251.3
	AGTPBP1	ENST00000337006.8	TSL:5	c.3660-5640C>A		intron	N/A	ENSP00000338512.5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42413 AN: 152008 Hom.: 8908 Cov.: 33

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.279 AC: 42497 AN: 152126 Hom.: 8939 Cov.: 33 AF XY: 0.279 AC XY: 20729 AN XY: 74378

African (AFR) AF: 0.574 AC: 23810 AN: 41494

American (AMR) AF: 0.168 AC: 2564 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2583 AN: 5172

South Asian (SAS) AF: 0.296 AC: 1429 AN: 4824

European-Finnish (FIN) AF: 0.127 AC: 1337 AN: 10566

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9532 AN: 67994

Other (OTH) AF: 0.236 AC: 499 AN: 2114

Alfa AF: 0.159 Hom.: 1165

Bravo AF: 0.295

Asia WGS AF: 0.358 AC: 1242 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.7
DANN	Benign	0.22
PhyloP100		0.15
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: rs10868320; hg19: chr9-88167841;