Genetic Variant AJAP1:p.Gly47Arg (chr1-4712009-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AJAP1	NM_018836.4 link	c.139G>A	p.Gly47Arg	missense_variant	Exon 2 of 6	ENST00000378191.5	NP_061324.1	Q9UKB5
AJAP1	NM_001042478.2 link	c.139G>A	p.Gly47Arg	missense_variant	Exon 2 of 6		NP_001035943.1	Q9UKB5
AJAP1	XM_011541786.3 link	c.139G>A	p.Gly47Arg	missense_variant	Exon 2 of 7		XP_011540088.1	Q9UKB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AJAP1	ENST00000378191.5 link	c.139G>A	p.Gly47Arg	missense_variant	Exon 2 of 6	1	NM_018836.4	ENSP00000367433.3	Q9UKB5
AJAP1	ENST00000378190.7 link	c.139G>A	p.Gly47Arg	missense_variant	Exon 2 of 6	5		ENSP00000367432.3	Q9UKB5
AJAP1	ENST00000466761.1 link	n.142G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.139G>A (p.G47R) alteration is located in exon 2 (coding exon 2) of the AJAP1 gene. This alteration results from a G to A substitution at nucleotide position 139, causing the glycine (G) at amino acid position 47 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

.;T

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.52

MutPred

0.42

Gain of solvent accessibility (P = 0.0328);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

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over