Genetic Variant AJAP1:p.Gly47Arg (chr1-4712009-G-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_018836.4(AJAP1):c.139G>A(p.Gly47Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G47E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AJAP1
NM_018836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.139G>A	p.Gly47Arg	missense	Exon 2 of 6	NP_061324.1	Q9UKB5
	AJAP1	NM_001042478.2		c.139G>A	p.Gly47Arg	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.139G>A	p.Gly47Arg	missense	Exon 2 of 6	ENSP00000367433.3	Q9UKB5
AJAP1	ENST00000378190.7	TSL:5	c.139G>A	p.Gly47Arg	missense	Exon 2 of 6	ENSP00000367432.3	Q9UKB5
AJAP1	ENST00000880749.1		c.139G>A	p.Gly47Arg	missense	Exon 2 of 5	ENSP00000550808.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1442934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717472

African (AFR)

AF:

0.00

AC:

AN:

31150

American (AMR)

AF:

0.00

AC:

AN:

42300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25520

East Asian (EAS)

AF:

0.00

AC:

AN:

37426

South Asian (SAS)

AF:

0.00

AC:

AN:

83586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105860

Other (OTH)

AF:

0.00

AC:

AN:

59658

GnomAD4 genome

Cov.:

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

0.22

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.1

PhyloP100

3.1

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.52

MutPred

0.42

Gain of solvent accessibility (P = 0.0328)

MVP

0.50

MPC

1.3

ClinPred

0.99

GERP RS

5.1

Varity_R

0.68

gMVP

0.58

Mutation Taster

=83/17

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

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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