Genetic Variant AJAP1:p.Ser166Arg (chr1-4712368-C-G) – 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.498C>G(p.Ser166Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: -0.140

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=0.096518934).

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.498C>G	p.Ser166Arg	missense	Exon 2 of 6	NP_061324.1	Q9UKB5
	AJAP1	NM_001042478.2		c.498C>G	p.Ser166Arg	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.498C>G	p.Ser166Arg	missense	Exon 2 of 6	ENSP00000367433.3	Q9UKB5
AJAP1	ENST00000378190.7	TSL:5	c.498C>G	p.Ser166Arg	missense	Exon 2 of 6	ENSP00000367432.3	Q9UKB5
AJAP1	ENST00000880749.1		c.498C>G	p.Ser166Arg	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:

1377784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676140

African (AFR)

AF:

0.00

AC:

AN:

31472

American (AMR)

AF:

0.00

AC:

AN:

34902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22176

East Asian (EAS)

AF:

0.00

AC:

AN:

36906

South Asian (SAS)

AF:

0.00

AC:

AN:

73410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5444

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068398

Other (OTH)

AF:

0.00

AC:

AN:

56904

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

0.23

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.028

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.48

M_CAP

Benign

0.0085

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.14

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

REVEL

Benign

0.043

Sift

Benign

0.28

Sift4G

Benign

0.17

Polyphen

0.57

Vest4

0.14

MutPred

0.20

Gain of MoRF binding (P = 0.0159)

MVP

0.30

MPC

0.62

ClinPred

0.46

GERP RS

2.3

Varity_R

0.064

gMVP

0.13

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over