Genetic Variant AJUBA:p.Cys476Ser (chr14-22974111-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032876.6(AJUBA):c.1427G>C(p.Cys476Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,614,176 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 2 hom. )

Consequence

AJUBA
NM_032876.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

Publications

5 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.035724968).

BS2

High AC in GnomAd4 at 63 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.1427G>C	p.Cys476Ser	missense	Exon 7 of 8	NP_116265.1	Q96IF1-1
	AJUBA	NM_198086.3		c.176G>C	p.Cys59Ser	missense	Exon 5 of 6	NP_932352.1	Q96IF1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AJUBA	ENST00000262713.7	TSL:1 MANE Select	c.1427G>C	p.Cys476Ser	missense	Exon 7 of 8	ENSP00000262713.2	Q96IF1-1
ENSG00000259132	ENST00000555074.1	TSL:2	c.49+8098G>C		intron	N/A	ENSP00000450856.2	G3V2T6
AJUBA	ENST00000397388.7	TSL:2	c.176G>C	p.Cys59Ser	missense	Exon 5 of 6	ENSP00000380543.3	Q96IF1-2

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000286

AC:

AN:

251434

AF XY:

0.000287

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000554

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000755

AC:

1103

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000696

AC XY:

506

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000941

AC:

1046

AN:

1111992

Other (OTH)

AF:

0.000811

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000414

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000853

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000558

Hom.:

Bravo

AF:

0.000363

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.13

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

M_CAP

Benign

0.0093

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.13

PhyloP100

0.85

PrimateAI

Uncertain

0.61

PROVEAN

Benign

1.2

REVEL

Benign

0.084

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.024

Vest4

0.24

MutPred

0.61

Gain of catalytic residue at L471 (P = 0.0016)

MVP

0.60

ClinPred

0.036

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.67

Mutation Taster

=84/16

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over