Genetic Variant AJUBA:p.Val288Met (chr14-22981405-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_032876.6(AJUBA):c.862G>A(p.Val288Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

AJUBA
NM_032876.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

Genes affected

AJUBA (HGNC:20250): (ajuba LIM protein) Enables alpha-catenin binding activity and transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; positive regulation of gene silencing by miRNA; and regulation of cellular response to hypoxia. Acts upstream of or within gene silencing by miRNA and positive regulation of protein-containing complex assembly. Located in several cellular components, including Golgi apparatus; P-body; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AJUBA links:

ENSG00000259132 (HGNC:):

ENSG00000259132 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28478596).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AJUBA	NM_032876.6 link	c.862G>A	p.Val288Met	missense_variant	Exon 1 of 8	ENST00000262713.7	NP_116265.1	Q96IF1-1
AJUBA	NM_001289097.2 link	c.862G>A	p.Val288Met	missense_variant	Exon 1 of 2		NP_001276026.1	Q96IF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AJUBA	ENST00000262713.7 link	c.862G>A	p.Val288Met	missense_variant	Exon 1 of 8	1	NM_032876.6	ENSP00000262713.2	Q96IF1-1
ENSG00000259132	ENST00000555074.1 link	c.49+804G>A		intron_variant	Intron 1 of 4	2		ENSP00000450856.2	G3V2T6
AJUBA	ENST00000553736.1 link	c.181G>A	p.Val61Met	missense_variant	Exon 1 of 2	2		ENSP00000451772.1	H0YJL9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244142

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133670

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 SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460288

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.862G>A (p.V288M) alteration is located in exon 1 (coding exon 1) of the AJUBA gene. This alteration results from a G to A substitution at nucleotide position 862, causing the valine (V) at amino acid position 288 to be replaced by a methionine (M). 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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.041

Sift

Benign

0.092

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.97

D;D

Vest4

0.13

MutPred

0.29

Gain of catalytic residue at T290 (P = 4e-04);Gain of catalytic residue at T290 (P = 4e-04);

MVP

0.70

ClinPred

0.38

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.082

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over