NM_001330701.2:c.3355G>A

Variant names:

• chr9-85575463-C-T
• rs767296418
• NM_001330701.2:c.3355G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330701.2(AGTPBP1):​c.3355G>A​(p.Gly1119Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000436 in 1,605,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AGTPBP1 NM_001330701.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59
• 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23866013).

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.3355G>A	p.Gly1119Ser	missense	Exon 25 of 26	NP_001317630.1	Q9UPW5-1
	AGTPBP1	NM_001286715.1		c.3511G>A	p.Gly1171Ser	missense	Exon 24 of 25	NP_001273644.1	J3KNS1
	AGTPBP1	NM_001286717.1		c.3391G>A	p.Gly1131Ser	missense	Exon 24 of 25	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.3355G>A	p.Gly1119Ser	missense	Exon 25 of 26	ENSP00000349592.3	Q9UPW5-1
	AGTPBP1	ENST00000376083.7	TSL:1	c.3235G>A	p.Gly1079Ser	missense	Exon 25 of 26	ENSP00000365251.3	Q9UPW5-2
	AGTPBP1	ENST00000337006.8	TSL:5	c.3511G>A	p.Gly1171Ser	missense	Exon 24 of 25	ENSP00000338512.5	J3KNS1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244210 AF XY: 0.00000757

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1453916 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 723080

African (AFR) AF: 0.00 AC: 0 AN: 33192

American (AMR) AF: 0.00 AC: 0 AN: 42614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39156

South Asian (SAS) AF: 0.00 AC: 0 AN: 83866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1109984

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152018 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74250

African (AFR) AF: 0.0000242 AC: 1 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.30	N
PhyloP100		3.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.087
Sift	Benign	0.067	T
Sift4G	Benign	0.21	T
Polyphen		0.36	B
Vest4		0.53
MutPred		0.56		Gain of phosphorylation at G1119 (P = 0.0895)
MVP		0.29
MPC		0.055
ClinPred		0.52	D
GERP RS		5.2
Varity_R		0.41
gMVP		0.63
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs767296418; hg19: chr9-88190378;