chr7-134993675-A-T

Position:

• chr7-134993675-A-T

Variant summary

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

The NM_178563.4(AGBL3):​c.307A>T​(p.Ile103Phe) variant causes a missense change. 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: AGBL3 NM_178563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58

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

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
AGBL3	NM_178563.4	c.307A>T	p.Ile103Phe	missense_variant	4/17	ENST00000436302.6	NP_848658.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL3	ENST00000436302.6	c.307A>T	p.Ile103Phe	missense_variant	4/17	2	NM_178563.4	ENSP00000388275.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.307A>T (p.I103F) alteration is located in exon 4 (coding exon 3) of the AGBL3 gene. This alteration results from a A to T substitution at nucleotide position 307, causing the isoleucine (I) at amino acid position 103 to be replaced by a phenylalanine (F). 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
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.76
MutPred		0.23		Gain of ubiquitination at K99 (P = 0.1008);Gain of ubiquitination at K99 (P = 0.1008);
MVP		0.092
ClinPred		0.98	D
GERP RS		5.7
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1810601230; hg19: chr7-134678426;