Variant chr14-22981545-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032876.6(AJUBA):c.722T>C(p.Leu241Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 7.0e-7 ( 0 hom. )

Consequence

AJUBA
NM_032876.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3750281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJUBA	NM_032876.6 linkuse as main transcript	c.722T>C	p.Leu241Pro	missense_variant	1/8	ENST00000262713.7	NP_116265.1	Q96IF1-1
AJUBA	NM_001289097.2 linkuse as main transcript	c.722T>C	p.Leu241Pro	missense_variant	1/2		NP_001276026.1	Q96IF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AJUBA	ENST00000262713.7 linkuse as main transcript	c.722T>C	p.Leu241Pro	missense_variant	1/8	1	NM_032876.6	ENSP00000262713.2	Q96IF1-1
ENSG00000259132	ENST00000555074.1 linkuse as main transcript	c.49+664T>C		intron_variant		2		ENSP00000450856.2	G3V2T6
AJUBA	ENST00000553736.1 linkuse as main transcript	c.41T>C	p.Leu14Pro	missense_variant	1/2	2		ENSP00000451772.1	H0YJL9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435358

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712646

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

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

Sep 14, 2023

The c.722T>C (p.L241P) alteration is located in exon 1 (coding exon 1) of the AJUBA gene. This alteration results from a T to C substitution at nucleotide position 722, causing the leucine (L) at amino acid position 241 to be replaced by a proline (P). 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

0.061

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.032

T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.65

.;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.48

N;N

REVEL

Benign

0.18

Sift

Benign

0.13

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.99

D;D

Vest4

0.51

MutPred

0.33

Gain of catalytic residue at V246 (P = 2e-04);Gain of catalytic residue at V246 (P = 2e-04);

MVP

0.83

ClinPred

0.46

GERP RS

4.7

Varity_R

0.22

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over