rs12286721

chr11-47679976-C-Achr11-47679976-C-Gchr11-47679976-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024783.4(AGBL2):c.2013G>T(p.Met671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,587,002 control chromosomes in the GnomAD database, including 253,138 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.59 (27002 hom., cov: 29)
  • Exomes 𝑓: 0.56 (226136 hom.)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6918674E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGBL2	NM_024783.4	c.2013G>T	p.Met671Ile	missense_variant	13/19	ENST00000525123.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGBL2	ENST00000525123.6	c.2013G>T	p.Met671Ile	missense_variant	13/19	1	NM_024783.4	P2
AGBL2	ENST00000528609.5	c.*140G>T		3_prime_UTR_variant, NMD_transcript_variant	3/9	1
AGBL2	ENST00000528244.5	c.1899G>T	p.Met633Ile	missense_variant	12/16	2		A2
AGBL2	ENST00000529712.5	n.2547G>T		non_coding_transcript_exon_variant	10/11	2

Frequencies

GnomAD3 genomes AF: 0.594 AC: 89788 AN: 151222 Hom.: 26979 Cov.: 29

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.559

GnomAD3 exomes AF: 0.581 AC: 144818 AN: 249432 Hom.: 43163 AF XY: 0.568 AC XY: 76574 AN XY: 134816

Gnomad AFR exome AF: 0.629

Gnomad AMR exome AF: 0.738

Gnomad ASJ exome AF: 0.508

Gnomad EAS exome AF: 0.609

Gnomad SAS exome AF: 0.459

Gnomad FIN exome AF: 0.657

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.557 AC: 799242 AN: 1435662 Hom.: 226136 Cov.: 26 AF XY: 0.553 AC XY: 395936 AN XY: 715812

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.727

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.647

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.594 AC: 89850 AN: 151340 Hom.: 27002 Cov.: 29 AF XY: 0.600 AC XY: 44315 AN XY: 73894

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.563

Alfa AF: 0.553 Hom.: 58748

Bravo AF: 0.599

TwinsUK AF: 0.551 AC: 2044

ALSPAC AF: 0.556 AC: 2143

ESP6500AA AF: 0.615 AC: 2709

ESP6500EA AF: 0.546 AC: 4694

ExAC AF: 0.572 AC: 69399

Asia WGS AF: 0.511 AC: 1779 AN: 3478

EpiCase AF: 0.543

EpiControl AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	16
Dann	Benign	0.88
DEOGEN2	Benign	0.0031	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.53	D
MetaRNN	Benign	0.0000027	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.079	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.015
MutPred		0.19		Gain of methylation at K672 (P = 0.0258);Gain of methylation at K672 (P = 0.0258);.;
MPC		0.12
ClinPred		0.0046	T
GERP RS		0.55
Varity_R		0.082
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs12286721; hg19: chr11-47701528; COSMIC: COSV54092398;