Variant 14-22981698-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032876.6(AJUBA):c.569G>A(p.Gly190Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,366,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

AJUBA
NM_032876.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.597

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11293855).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJUBA	NM_032876.6 linkuse as main transcript	c.569G>A	p.Gly190Glu	missense_variant	1/8	ENST00000262713.7	NP_116265.1	Q96IF1-1
AJUBA	NM_001289097.2 linkuse as main transcript	c.569G>A	p.Gly190Glu	missense_variant	1/2		NP_001276026.1	Q96IF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJUBA	ENST00000262713.7 linkuse as main transcript	c.569G>A	p.Gly190Glu	missense_variant	1/8	1	NM_032876.6	ENSP00000262713.2		Q96IF1-1
ENSG00000259132	ENST00000555074.1 linkuse as main transcript	c.49+511G>A		intron_variant		2		ENSP00000450856.2		G3V2T6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000847

AC:

AN:

118010

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

64214

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000226

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000805

AC:

AN:

1366686

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

672544

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:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000655

Gnomad4 OTH exome

AF:

0.0000527

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2024

The c.569G>A (p.G190E) 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 569, causing the glycine (G) at amino acid position 190 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.063

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.71

.;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.41

T;T

Polyphen

0.0080

B;B

Vest4

0.17

MutPred

0.29

Gain of catalytic residue at Y195 (P = 6e-04);Gain of catalytic residue at Y195 (P = 6e-04);

MVP

0.28

ClinPred

0.099

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.095

gMVP

0.76

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