1-4712386-C-G

Position:

• chr1-4712386-C-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.516C>G​(p.Ser172Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000714 in 1,401,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: AJAP1 NM_018836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.924

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=0.13933498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AJAP1	NM_018836.4	c.516C>G	p.Ser172Arg	missense_variant	2/6	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.516C>G	p.Ser172Arg	missense_variant	2/6		NP_001035943.1
AJAP1	XM_011541786.3	c.516C>G	p.Ser172Arg	missense_variant	2/7		XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.516C>G	p.Ser172Arg	missense_variant	2/6	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.516C>G	p.Ser172Arg	missense_variant	2/6	5		ENSP00000367432.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000714 AC: 10 AN: 1401342 Hom.: 0 Cov.: 37 AF XY: 0.00000869 AC XY: 6 AN XY: 690610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000527

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: 0.00000741

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2024

The c.516C>G (p.S172R) alteration is located in exon 2 (coding exon 2) of the AJAP1 gene. This alteration results from a C to G substitution at nucleotide position 516, causing the serine (S) at amino acid position 172 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.11
Sift	Benign	0.060	T;T
Sift4G	Benign	0.066	T;T
Polyphen		0.51	P;P
Vest4		0.13
MutPred		0.14		Loss of phosphorylation at S172 (P = 0.0096);Loss of phosphorylation at S172 (P = 0.0096);
MVP		0.29
MPC		0.51
ClinPred		0.22	T
GERP RS		4.3
Varity_R		0.24
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs1340787438; hg19: chr1-4772446;