NM_032785.4:c.952-10357A>G

Variant names:

• chr1-48601342-T-C
• rs12127450
• NM_032785.4:c.952-10357A>G

Variant summary

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

The NM_032785.4(AGBL4):​c.952-10357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,250 control chromosomes in the GnomAD database, including 1,488 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 0.13 (1488 hom., cov: 33)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 2 publications found

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

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 (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032785.4. 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
	AGBL4	NM_032785.4	MANE Select	c.952-10357A>G		intron	N/A	NP_116174.3
	AGBL4	NM_001323574.2		c.988-10357A>G		intron	N/A	NP_001310503.1
	AGBL4	NM_001323573.2		c.988-10357A>G		intron	N/A	NP_001310502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.952-10357A>G		intron	N/A	ENSP00000360905.1
	AGBL4	ENST00000416121.5	TSL:1	c.487-10357A>G		intron	N/A	ENSP00000401622.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20089 AN: 152130 Hom.: 1491 Cov.: 33

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.132 AC: 20087 AN: 152250 Hom.: 1488 Cov.: 33 AF XY: 0.130 AC XY: 9646 AN XY: 74430

African (AFR) AF: 0.0848 AC: 3524 AN: 41562

American (AMR) AF: 0.101 AC: 1544 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5182

South Asian (SAS) AF: 0.179 AC: 861 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10602

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11688 AN: 68008

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.160 Hom.: 3788

Bravo AF: 0.126

Asia WGS AF: 0.0720 AC: 254 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	0.25
DANN	Benign	0.70
PhyloP100		-0.72
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: rs12127450; hg19: chr1-49067014; COSMIC: COSV61891487;