Variant 11-47690085-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024783.4(AGBL2):c.1622T>C(p.Met541Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 8.73

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.925

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL2	NM_024783.4 link	c.1622T>C	p.Met541Thr	missense_variant	10/19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AGBL2	ENST00000525123.6 link	c.1622T>C	p.Met541Thr	missense_variant	10/19	1	NM_024783.4	ENSP00000435582.1	Q5U5Z8-1
AGBL2	ENST00000528244.5 link	c.1508T>C	p.Met503Thr	missense_variant	9/16	2		ENSP00000436630.1	F6U0I4
AGBL2	ENST00000528609.5 link	n.284T>C		non_coding_transcript_exon_variant	1/9	1		ENSP00000431912.1	J9JIH1
AGBL2	ENST00000529712.5 link	n.2156T>C		non_coding_transcript_exon_variant	7/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721336

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2023

The c.1622T>C (p.M541T) alteration is located in exon 10 (coding exon 9) of the AGBL2 gene. This alteration results from a T to C substitution at nucleotide position 1622, causing the methionine (M) at amino acid position 541 to be replaced by a threonine (T). 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

0.54

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.051

T;.;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.0

M;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.77

P;.;D

Vest4

0.90

MutPred

0.78

Gain of phosphorylation at M541 (P = 0.0543);Gain of phosphorylation at M541 (P = 0.0543);.;

MVP

0.41

MPC

0.57

ClinPred

0.87

GERP RS

6.0

Varity_R

0.65

gMVP

0.90

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