chr14-22981279-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032876.6(AJUBA):​c.988G>A​(p.Ala330Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,956 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. 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. A330P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AJUBA
NM_032876.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059367746).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AJUBANM_032876.6 linkc.988G>A p.Ala330Thr missense_variant Exon 1 of 8 ENST00000262713.7 NP_116265.1 Q96IF1-1
AJUBANM_001289097.2 linkc.988G>A p.Ala330Thr missense_variant Exon 1 of 2 NP_001276026.1 Q96IF1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AJUBAENST00000262713.7 linkc.988G>A p.Ala330Thr missense_variant Exon 1 of 8 1 NM_032876.6 ENSP00000262713.2 Q96IF1-1
ENSG00000259132ENST00000555074.1 linkc.49+930G>A intron_variant Intron 1 of 4 2 ENSP00000450856.2 G3V2T6
AJUBAENST00000553736.1 linkc.307G>A p.Ala103Thr missense_variant Exon 1 of 2 2 ENSP00000451772.1 H0YJL9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457956
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
724672
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:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.032
T;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.61
.;T
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.70
N;N
REVEL
Benign
0.042
Sift
Benign
0.21
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;B
Vest4
0.061
MutPred
0.33
Gain of phosphorylation at A330 (P = 0.0076);Gain of phosphorylation at A330 (P = 0.0076);
MVP
0.47
ClinPred
0.088
T
GERP RS
-0.27
Varity_R
0.078
gMVP
0.31

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.

Other links and lift over

hg19: chr14-23450488; API