Genetic Variant NM_032785.4:c.931G>A (chr1-48634513-C-T) – 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>A(p.Val311Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

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:

Genome browser will be placed here

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=0.043318033).

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>A	p.Val311Ile	missense	Exon 9 of 14	NP_116174.3	Q5VU57-1
AGBL4	NM_001323574.2		c.967G>A	p.Val323Ile	missense	Exon 9 of 14	NP_001310503.1
AGBL4	NM_001323573.2		c.967G>A	p.Val323Ile	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>A	p.Val311Ile	missense	Exon 9 of 14	ENSP00000360905.1	Q5VU57-1
AGBL4	ENST00000416121.5	TSL:1	c.466G>A	p.Val156Ile	missense	Exon 5 of 7	ENSP00000401622.1	H0Y5X4
AGBL4	ENST00000371838.5	TSL:5	c.931G>A	p.Val311Ile	missense	Exon 9 of 9	ENSP00000360904.1	B1AMW3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000430

AC:

AN:

232338

AF XY:

0.00000798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

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

AF:

0.00000138

AC:

AN:

1450114

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719956

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33310

American (AMR)

AF:

0.00

AC:

AN:

43474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.00

AC:

AN:

83570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106142

Other (OTH)

AF:

0.0000167

AC:

AN:

59986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

0.074

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.26

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0038

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.64

M_CAP

Benign

0.0056

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

-0.26

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.15

REVEL

Benign

0.042

Sift

Benign

0.31

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.051

MutPred

0.46

Loss of ubiquitination at K307 (P = 0.0699)

MVP

0.014

MPC

0.10

ClinPred

0.054

GERP RS

-5.1

Varity_R

0.030

gMVP

0.067

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over