NM_024783.4:c.1595T>A

Variant names:

• chr11-47690112-A-T
• NM_024783.4:c.1595T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024783.4(AGBL2):​c.1595T>A​(p.Phe532Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,490 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• Publications: 0 publications found

Genes affected

AGBL2 (HGNC:26296): (AGBL carboxypeptidase 2) Predicted to enable metallocarboxypeptidase activity. Predicted to be involved in protein side chain deglutamylation. Located in centriole and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

AGBL2 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38654003).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024783.4. 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
	AGBL2	NM_024783.4	MANE Select	c.1595T>A	p.Phe532Tyr	missense	Exon 10 of 19	NP_079059.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL2	ENST00000525123.6	TSL:1 MANE Select	c.1595T>A	p.Phe532Tyr	missense	Exon 10 of 19	ENSP00000435582.1	Q5U5Z8-1
	AGBL2	ENST00000528244.5	TSL:2	c.1481T>A	p.Phe494Tyr	missense	Exon 9 of 16	ENSP00000436630.1	F6U0I4
	AGBL2	ENST00000528609.5	TSL:1	n.257T>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000431912.1	J9JIH1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459490 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725984

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 43966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 85630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111438

Other (OTH) AF: 0.00 AC: 0 AN: 60306

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.048
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.23	T
Sift4G	Benign	0.28	T
Polyphen		0.12	B
Vest4		0.44
MutPred		0.55		Loss of MoRF binding (P = 0.1556)
MVP		0.28
MPC		0.50
ClinPred		0.90	D
GERP RS		6.0
Varity_R		0.28
gMVP		0.76
Mutation Taster		=49/51	disease causing

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

hg19: chr11-47711664;