Variant 14-22981318-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.949G>A(p.Val317Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000041 ( 0 hom. )

Consequence

AJUBA
NM_032876.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

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:

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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=0.06850192).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJUBA	NM_032876.6 linkuse as main transcript	c.949G>A	p.Val317Ile	missense_variant	1/8	ENST00000262713.7	NP_116265.1
AJUBA	NM_001289097.2 linkuse as main transcript	c.949G>A	p.Val317Ile	missense_variant	1/2		NP_001276026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJUBA	ENST00000262713.7 linkuse as main transcript	c.949G>A	p.Val317Ile	missense_variant	1/8	1	NM_032876.6	ENSP00000262713	P1	Q96IF1-1
AJUBA	ENST00000553736.1 linkuse as main transcript	c.271G>A	p.Val91Ile	missense_variant	1/2	2		ENSP00000451772

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459816

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725900

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 20, 2024

The c.949G>A (p.V317I) 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 949, causing the valine (V) at amino acid position 317 to be replaced by an isoleucine (I). 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

0.079

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.19

N;N

REVEL

Benign

0.083

Sift

Benign

0.090

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.18

B;B

Vest4

0.050

MutPred

0.28

Gain of catalytic residue at P312 (P = 0);Gain of catalytic residue at P312 (P = 0);

MVP

0.35

ClinPred

0.13

GERP RS

3.3

Varity_R

0.044

gMVP

0.26

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