rs886886319

Variant names:

• chr1-48587162-C-T
• rs886886319
• NM_032785.4:c.1109G>A

Variant summary

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

The NM_032785.4(AGBL4):​c.1109G>A​(p.Ser370Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,399,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AGBL4 NM_032785.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• Publications: 0 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: 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=0.13765478).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	NM_032785.4	MANE Select	c.1109G>A	p.Ser370Asn	missense	Exon 11 of 14	NP_116174.3	Q5VU57-1
	AGBL4	NM_001323574.2		c.1145G>A	p.Ser382Asn	missense	Exon 11 of 14	NP_001310503.1
	AGBL4	NM_001323573.2		c.1145G>A	p.Ser382Asn	missense	Exon 11 of 13	NP_001310502.1	Q5VU57-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.1109G>A	p.Ser370Asn	missense	Exon 11 of 14	ENSP00000360905.1	Q5VU57-1
	AGBL4	ENST00000416121.5	TSL:1	c.644G>A	p.Ser215Asn	missense	Exon 7 of 7	ENSP00000401622.1	H0Y5X4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690482

African (AFR) AF: 0.00 AC: 0 AN: 31672

American (AMR) AF: 0.00 AC: 0 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25038

East Asian (EAS) AF: 0.00 AC: 0 AN: 35804

South Asian (SAS) AF: 0.00 AC: 0 AN: 79108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079406

Other (OTH) AF: 0.00 AC: 0 AN: 58070

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	21
DANN	Benign	0.81
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.088
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.29	N
PhyloP100		3.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.087
Sift	Benign	1.0	T
Sift4G	Benign	0.81	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.076
MPC		0.12
ClinPred		0.82	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.29
Mutation Taster		=89/11	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: rs886886319; hg19: chr1-49052834;