1-4712124-G-C

Variant names:

• chr1-4712124-G-C
• rs765357051
• NM_018836.4:c.254G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018836.4(AJAP1):​c.254G>C​(p.Arg85Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R85L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AJAP1 NM_018836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 4 publications found

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

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=0.23655266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.254G>C	p.Arg85Pro	missense_variant	Exon 2 of 6	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.254G>C	p.Arg85Pro	missense_variant	Exon 2 of 6		NP_001035943.1
AJAP1	XM_011541786.3	c.254G>C	p.Arg85Pro	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.254G>C	p.Arg85Pro	missense_variant	Exon 2 of 6	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.254G>C	p.Arg85Pro	missense_variant	Exon 2 of 6	5		ENSP00000367432.3
AJAP1	ENST00000466761.1	n.257G>C		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PhyloP100		0.25
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.16
Sift	Benign	0.20	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.99	D;D
Vest4		0.37
MutPred		0.31		Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);
MVP		0.54
MPC		0.58
ClinPred		0.38	T
GERP RS		2.3
Varity_R		0.23
gMVP		0.26
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs765357051; hg19: chr1-4772184;