chr14-22981492-G-T

Variant names:

• chr14-22981492-G-T
• rs529090199
• NM_032876.6:c.775C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032876.6(AJUBA):​c.775C>A​(p.Pro259Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000457 in 1,595,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: AJUBA NM_032876.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.793
• Publications: 0 publications found

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:):

AJUBA-DT (HGNC:55449): (AJUBA divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018121868).
• BS2: High AC in GnomAd4 at 43 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032876.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AJUBA	NM_032876.6	MANE Select	c.775C>A	p.Pro259Thr	missense	Exon 1 of 8	NP_116265.1	Q96IF1-1
	AJUBA	NM_001289097.2		c.775C>A	p.Pro259Thr	missense	Exon 1 of 2	NP_001276026.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AJUBA	ENST00000262713.7	TSL:1 MANE Select	c.775C>A	p.Pro259Thr	missense	Exon 1 of 8	ENSP00000262713.2	Q96IF1-1
	ENSG00000259132	ENST00000555074.1	TSL:2	c.49+717C>A		intron	N/A	ENSP00000450856.2	G3V2T6
	AJUBA	ENST00000921862.1		c.775C>A	p.Pro259Thr	missense	Exon 1 of 7	ENSP00000591921.1

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 43 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000682 AC: 14 AN: 205352 AF XY: 0.0000352

Gnomad AFR exome AF: 0.00104

Gnomad AMR exome AF: 0.0000641

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000208 AC: 30 AN: 1443350 Hom.: 0 Cov.: 31 AF XY: 0.0000167 AC XY: 12 AN XY: 717142

African (AFR) AF: 0.000812 AC: 27 AN: 33244

American (AMR) AF: 0.0000234 AC: 1 AN: 42820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25748

East Asian (EAS) AF: 0.00 AC: 0 AN: 39004

South Asian (SAS) AF: 0.00 AC: 0 AN: 84578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105252

Other (OTH) AF: 0.0000335 AC: 2 AN: 59706

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74496

African (AFR) AF: 0.00103 AC: 43 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000336

ExAC AF: 0.0000505 AC: 6

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.043
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.79
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.033
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.26	T
Polyphen		0.063	B
Vest4		0.32
MVP		0.56
ClinPred		0.040	T
GERP RS		3.8
PromoterAI		-0.017	Neutral
Varity_R		0.13
gMVP		0.37
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs529090199; hg19: chr14-23450701;