9-85603900-A-G

Variant names:

• chr9-85603900-A-G
• rs11141033
• NM_001330701.2:c.2336-7451T>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.2336-7451T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,810 control chromosomes in the GnomAD database, including 3,661 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 0.19 (3661 hom., cov: 32)
• Consequence: AGTPBP1 NM_001330701.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTPBP1	NM_001330701.2	c.2336-7451T>C		intron_variant	Intron 17 of 25	ENST00000357081.8	NP_001317630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTPBP1	ENST00000357081.8	c.2336-7451T>C		intron_variant	Intron 17 of 25	5	NM_001330701.2	ENSP00000349592.3
AGTPBP1	ENST00000376083.7	c.2216-7451T>C		intron_variant	Intron 17 of 25	1		ENSP00000365251.3
AGTPBP1	ENST00000337006.8	c.2492-7451T>C		intron_variant	Intron 16 of 24	5		ENSP00000338512.5
AGTPBP1	ENST00000628899.1	c.2372-7451T>C		intron_variant	Intron 16 of 24	2		ENSP00000487074.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29290 AN: 151692 Hom.: 3653 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.193 AC: 29308 AN: 151810 Hom.: 3661 Cov.: 32 AF XY: 0.199 AC XY: 14782 AN XY: 74216

African (AFR) AF: 0.0469 AC: 1942 AN: 41398

American (AMR) AF: 0.314 AC: 4792 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1159 AN: 3464

East Asian (EAS) AF: 0.124 AC: 628 AN: 5080

South Asian (SAS) AF: 0.341 AC: 1641 AN: 4816

European-Finnish (FIN) AF: 0.282 AC: 2985 AN: 10576

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15302 AN: 67894

Other (OTH) AF: 0.225 AC: 474 AN: 2106

Alfa AF: 0.103 Hom.: 113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		0.24
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: rs11141033; hg19: chr9-88218815; COSMIC: COSV61276710;