11-47690112-A-T

Position:

• chr11-47690112-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL2	NM_024783.4	c.1595T>A	p.Phe532Tyr	missense_variant	10/19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6	c.1595T>A	p.Phe532Tyr	missense_variant	10/19	1	NM_024783.4	ENSP00000435582.1
AGBL2	ENST00000528244.5	c.1481T>A	p.Phe494Tyr	missense_variant	9/16	2		ENSP00000436630.1
AGBL2	ENST00000528609.5	n.257T>A		non_coding_transcript_exon_variant	1/9	1		ENSP00000431912.1
AGBL2	ENST00000529712.5	n.2129T>A		non_coding_transcript_exon_variant	7/11	2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2022

The c.1595T>A (p.F532Y) alteration is located in exon 10 (coding exon 9) of the AGBL2 gene. This alteration results from a T to A substitution at nucleotide position 1595, causing the phenylalanine (F) at amino acid position 532 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.12	B;.;B
Vest4		0.44
MutPred		0.55		Loss of MoRF binding (P = 0.1556);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47711664;