1-4712180-C-G

Variant names:

• chr1-4712180-C-G
• NM_018836.4:c.310C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018836.4(AJAP1):​c.310C>G​(p.Pro104Ala) 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. 12/21 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)
• Consequence: AJAP1 NM_018836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17734322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.310C>G	p.Pro104Ala	missense_variant	Exon 2 of 6	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.310C>G	p.Pro104Ala	missense_variant	Exon 2 of 6		NP_001035943.1
AJAP1	XM_011541786.3	c.310C>G	p.Pro104Ala	missense_variant	Exon 2 of 7		XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.310C>G	p.Pro104Ala	missense_variant	Exon 2 of 6	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.310C>G	p.Pro104Ala	missense_variant	Exon 2 of 6	5		ENSP00000367432.3
AJAP1	ENST00000466761.1	n.*15C>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 104 of the AJAP1 protein (p.Pro104Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AJAP1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.052
Sift	Benign	0.083	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.57	P;P
Vest4		0.11
MutPred		0.21		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.33
MPC		0.95
ClinPred		0.61	D
GERP RS		4.2
Varity_R		0.13
gMVP		0.34

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.

Other links and lift over

hg19: chr1-4772240;