2-27052990-G-A

Position:

• chr2-27052990-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021831.6(AGBL5):​c.32G>A​(p.Ser11Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGBL5 NM_021831.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.20

Genes affected

AGBL5 (HGNC:26147): (AGBL carboxypeptidase 5) This gene encodes a metallocarboxypeptidase involved in protein deglutamylation and a member of the peptidase M14 family of proteins. The encoded protein has been described as a "dual-functional" deglutamylase that can remove glutamate residues from both carboxyl termini and side chains of protein substrates. This deglutamylase activity may be important in antiviral immunity. Mutations in this gene are associated with retinitis pigmentosa. [provided by RefSeq, Jul 2016]

AGBL5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL5	NM_021831.6	c.32G>A	p.Ser11Asn	missense_variant	2/15	ENST00000360131.5	NP_068603.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL5	ENST00000360131.5	c.32G>A	p.Ser11Asn	missense_variant	2/15	1	NM_021831.6	ENSP00000353249.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.32G>A (p.S11N) alteration is located in exon 2 (coding exon 1) of the AGBL5 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the serine (S) at amino acid position 11 to be replaced by an asparagine (N). 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	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	.;.;.;.;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	1.9	.;.;.;L;L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N
REVEL	Uncertain	0.52
Sift	Benign	0.032	D;T;D;T;.;.
Sift4G	Uncertain	0.011	D;T;D;T;T;D
Polyphen		1.0	.;.;.;D;D;.
Vest4		0.68, 0.53
MutPred		0.38		Loss of phosphorylation at S11 (P = 0.0365);Loss of phosphorylation at S11 (P = 0.0365);Loss of phosphorylation at S11 (P = 0.0365);Loss of phosphorylation at S11 (P = 0.0365);Loss of phosphorylation at S11 (P = 0.0365);Loss of phosphorylation at S11 (P = 0.0365);
MVP		0.70
MPC		0.66
ClinPred		0.95	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr2-27275858;