dbSNP rs1019330654: AJUBA:p.Gly198* (chr14-22981675-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032876.6(AJUBA):c.592G>T(p.Gly198*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

AJUBA
NM_032876.6 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78

Publications

0 publications found

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:

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

AJUBA-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.592G>T	p.Gly198*	stop_gained	Exon 1 of 8	NP_116265.1	Q96IF1-1
	AJUBA	NM_001289097.2		c.592G>T	p.Gly198*	stop_gained	Exon 1 of 2	NP_001276026.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AJUBA	ENST00000262713.7	TSL:1 MANE Select	c.592G>T	p.Gly198*	stop_gained	Exon 1 of 8	ENSP00000262713.2	Q96IF1-1
ENSG00000259132	ENST00000555074.1	TSL:2	c.49+534G>T		intron	N/A	ENSP00000450856.2	G3V2T6
AJUBA	ENST00000921862.1		c.592G>T	p.Gly198*	stop_gained	Exon 1 of 7	ENSP00000591921.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.33e-7

AC:

AN:

1364208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670570

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31158

American (AMR)

AF:

0.00

AC:

AN:

33500

Ashkenazi Jewish (ASJ)

AF:

0.0000429

AC:

AN:

23326

East Asian (EAS)

AF:

0.00

AC:

AN:

35668

South Asian (SAS)

AF:

0.00

AC:

AN:

75378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066628

Other (OTH)

AF:

0.00

AC:

AN:

56732

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.47

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.62

PhyloP100

1.8

Vest4

0.77

GERP RS

2.8

PromoterAI

-0.0053

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=28/172

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over