chr14-22981279-C-T

Variant names:

• chr14-22981279-C-T
• NM_032876.6:c.988G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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]

ENSG00000259132 (HGNC:):

ACMG classification

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
AJUBA	NM_032876.6	c.988G>A	p.Ala330Thr	missense_variant	Exon 1 of 8	ENST00000262713.7	NP_116265.1
AJUBA	NM_001289097.2	c.988G>A	p.Ala330Thr	missense_variant	Exon 1 of 2		NP_001276026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AJUBA	ENST00000262713.7	c.988G>A	p.Ala330Thr	missense_variant	Exon 1 of 8	1	NM_032876.6	ENSP00000262713.2
ENSG00000259132	ENST00000555074.1	c.49+930G>A		intron_variant	Intron 1 of 4	2		ENSP00000450856.2
AJUBA	ENST00000553736.1	c.307G>A	p.Ala103Thr	missense_variant	Exon 1 of 2	2		ENSP00000451772.1

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

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;