Genetic Variant AJAP1:p.Ser135Leu (chr1-4712274-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018836.4(AJAP1):c.404C>T(p.Ser135Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,513,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

AJAP1
NM_018836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Publications

0 publications found

Variant links:

Genes affected

AJAP1 (HGNC:30801): (adherens junctions associated protein 1) Enables beta-catenin binding activity. Involved in negative regulation of cell-matrix adhesion; negative regulation of wound healing; and regulation of polarized epithelial cell differentiation. Located in several cellular components, including adherens junction; basolateral plasma membrane; and cell-cell contact zone. Is spanning component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AJAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0862121).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018836.4. 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
	AJAP1	NM_018836.4	MANE Select	c.404C>T	p.Ser135Leu	missense	Exon 2 of 6	NP_061324.1	Q9UKB5
	AJAP1	NM_001042478.2		c.404C>T	p.Ser135Leu	missense	Exon 2 of 6	NP_001035943.1	Q9UKB5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AJAP1	ENST00000378191.5	TSL:1 MANE Select	c.404C>T	p.Ser135Leu	missense	Exon 2 of 6	ENSP00000367433.3	Q9UKB5
AJAP1	ENST00000378190.7	TSL:5	c.404C>T	p.Ser135Leu	missense	Exon 2 of 6	ENSP00000367432.3	Q9UKB5
AJAP1	ENST00000880749.1		c.404C>T	p.Ser135Leu	missense	Exon 2 of 5	ENSP00000550808.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000689

AC:

AN:

145172

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1361212

Hom.:

Cov.:

AF XY:

0.00000899

AC XY:

AN XY:

667506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30286

American (AMR)

AF:

0.0000328

AC:

AN:

30464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20502

East Asian (EAS)

AF:

0.00

AC:

AN:

37686

South Asian (SAS)

AF:

0.00

AC:

AN:

70024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5352

European-Non Finnish (NFE)

AF:

0.0000103

AC:

AN:

1066654

Other (OTH)

AF:

0.0000535

AC:

AN:

56056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41596

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000843

AC:

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

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.70

M_CAP

Benign

0.0047

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.062

Sift

Benign

0.12

Sift4G

Benign

0.13

Polyphen

0.31

Vest4

0.21

MutPred

0.13

Loss of phosphorylation at S135 (P = 9e-04)

MVP

0.33

MPC

0.39

ClinPred

0.13

GERP RS

3.3

Varity_R

0.074

gMVP

0.15

Mutation Taster

=95/5

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