7-134993583-C-T

Variant names:

• chr7-134993583-C-T
• rs369701730
• NM_178563.4:c.215C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178563.4(AGBL3):​c.215C>T​(p.Pro72Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,399,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AGBL3 NM_178563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

Genes affected

AGBL3 (HGNC:27981): (AGBL carboxypeptidase 3) Enables metallocarboxypeptidase activity. Involved in protein side chain deglutamylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286458 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178563.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL3	NM_178563.4	MANE Select	c.215C>T	p.Pro72Leu	missense	Exon 4 of 17	NP_848658.3	Q8NEM8-4
	AGBL3	NM_001367812.1		c.215C>T	p.Pro72Leu	missense	Exon 4 of 5	NP_001354741.1
	AGBL3	NM_001367813.1		c.215C>T	p.Pro72Leu	missense	Exon 4 of 5	NP_001354742.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL3	ENST00000436302.6	TSL:2 MANE Select	c.215C>T	p.Pro72Leu	missense	Exon 4 of 17	ENSP00000388275.2	Q8NEM8-4
	AGBL3	ENST00000275763.10	TSL:1	n.215C>T		non_coding_transcript_exon	Exon 4 of 17	ENSP00000275763.6	Q8NEM8-2
	AGBL3	ENST00000435976.6	TSL:5	c.215C>T	p.Pro72Leu	missense	Exon 4 of 16	ENSP00000401220.2	F8W7R4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399702 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690340

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079002

Other (OTH) AF: 0.00 AC: 0 AN: 58128

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.19
Sift	Benign	0.036	D
Sift4G	Benign	0.064	T
Polyphen		0.96	D
Vest4		0.62
MutPred		0.41		Loss of disorder (P = 0.0345)
MVP		0.21
ClinPred		1.0	D
GERP RS		5.7
gMVP		0.76
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs369701730; hg19: chr7-134678334; COSMIC: COSV51949807;