Genetic Variant AGBL4:p.Val311Leu (chr1-48634513-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032785.4(AGBL4):c.931G>C(p.Val311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V311F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

AGBL4
NM_032785.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.262

Publications

7 publications found

Variant links:

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

AGBL4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046693772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032785.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGBL4	NM_032785.4	MANE Select	c.931G>C	p.Val311Leu	missense	Exon 9 of 14	NP_116174.3	Q5VU57-1
AGBL4	NM_001323574.2		c.967G>C	p.Val323Leu	missense	Exon 9 of 14	NP_001310503.1
AGBL4	NM_001323573.2		c.967G>C	p.Val323Leu	missense	Exon 9 of 13	NP_001310502.1	Q5VU57-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.931G>C	p.Val311Leu	missense	Exon 9 of 14	ENSP00000360905.1	Q5VU57-1
AGBL4	ENST00000416121.5	TSL:1	c.466G>C	p.Val156Leu	missense	Exon 5 of 7	ENSP00000401622.1	H0Y5X4
AGBL4	ENST00000371838.5	TSL:5	c.931G>C	p.Val311Leu	missense	Exon 9 of 9	ENSP00000360904.1	B1AMW3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000430

AC:

AN:

232338

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.41

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0033

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.79

M_CAP

Benign

0.0099

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.26

PrimateAI

Benign

0.32

PROVEAN

Benign

0.27

REVEL

Benign

0.039

Sift

Benign

0.39

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.21

MutPred

0.44

Loss of methylation at K307 (P = 0.1073)

MVP

0.014

MPC

0.13

ClinPred

0.037

GERP RS

-5.1

Varity_R

0.040

gMVP

0.18

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over