Variant 11-47690112-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
AGBL2	NM_024783.4 link	c.1595T>A	p.Phe532Tyr	missense_variant	Exon 10 of 19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGBL2	ENST00000525123.6 link	c.1595T>A	p.Phe532Tyr	missense_variant	Exon 10 of 19	1	NM_024783.4	ENSP00000435582.1	Q5U5Z8-1
AGBL2	ENST00000528244.5 link	c.1481T>A	p.Phe494Tyr	missense_variant	Exon 9 of 16	2		ENSP00000436630.1	F6U0I4
AGBL2	ENST00000528609.5 link	n.257T>A		non_coding_transcript_exon_variant	Exon 1 of 9	1		ENSP00000431912.1	J9JIH1
AGBL2	ENST00000529712.5 link	n.2129T>A		non_coding_transcript_exon_variant	Exon 7 of 11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459490

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725984

show subpopulations

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.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.010

T;.;.

Eigen

Benign

0.048

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.0058

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Uncertain

0.67

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over