rs754823601

Variant names:

• chr1-4712268-C-A
• rs754823601
• NM_018836.4:c.398C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-4712268-C-A
• chr1-4712268-C-G
• chr1-4712268-C-T

Variant summary

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

The NM_018836.4(AJAP1):​c.398C>A​(p.Ser133*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: AJAP1 NM_018836.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 0 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 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	c.398C>A	p.Ser133*	stop_gained	Exon 2 of 6	ENST00000378191.5	NP_061324.1
AJAP1	NM_001042478.2	c.398C>A	p.Ser133*	stop_gained	Exon 2 of 6		NP_001035943.1
AJAP1	XM_011541786.3	c.398C>A	p.Ser133*	stop_gained	Exon 2 of 7		XP_011540088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AJAP1	ENST00000378191.5	c.398C>A	p.Ser133*	stop_gained	Exon 2 of 6	1	NM_018836.4	ENSP00000367433.3
AJAP1	ENST00000378190.7	c.398C>A	p.Ser133*	stop_gained	Exon 2 of 6	5		ENSP00000367432.3
AJAP1	ENST00000466761.1	n.*103C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356074 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 664738

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30162

American (AMR) AF: 0.00 AC: 0 AN: 29812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20352

East Asian (EAS) AF: 0.00 AC: 0 AN: 37508

South Asian (SAS) AF: 0.00 AC: 0 AN: 69470

European-Finnish (FIN) AF: 0.0000233 AC: 1 AN: 42986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064552

Other (OTH) AF: 0.00 AC: 0 AN: 55892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.39	N
PhyloP100		2.4
Vest4		0.28
GERP RS		3.7
Mutation Taster		=16/184	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754823601; hg19: chr1-4772328;