GeneBe

NM_018836.4:c.516C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_018836.4(AJAP1):​c.516C>T​(p.Ser172Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

AJAP1
NM_018836.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.924

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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP7
Synonymous conserved (PhyloP=0.924 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AJAP1NM_018836.4 linkc.516C>T p.Ser172Ser synonymous_variant Exon 2 of 6 ENST00000378191.5 NP_061324.1 Q9UKB5
AJAP1NM_001042478.2 linkc.516C>T p.Ser172Ser synonymous_variant Exon 2 of 6 NP_001035943.1 Q9UKB5
AJAP1XM_011541786.3 linkc.516C>T p.Ser172Ser synonymous_variant Exon 2 of 7 XP_011540088.1 Q9UKB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AJAP1ENST00000378191.5 linkc.516C>T p.Ser172Ser synonymous_variant Exon 2 of 6 1 NM_018836.4 ENSP00000367433.3 Q9UKB5
AJAP1ENST00000378190.7 linkc.516C>T p.Ser172Ser synonymous_variant Exon 2 of 6 5 ENSP00000367432.3 Q9UKB5
AJAP1ENST00000466761.1 linkn.*221C>T downstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.14e-7
AC:
1
AN:
1401336
Hom.:
0
Cov.:
37
AF XY:
0.00000145
AC XY:
1
AN XY:
690604
show subpopulations
⚠️ 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:
31970
American (AMR)
AF:
0.00
AC:
0
AN:
37946
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23284
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77344
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49492
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5542
European-Non Finnish (NFE)
AF:
9.26e-7
AC:
1
AN:
1080322
Other (OTH)
AF:
0.00
AC:
0
AN:
57738
⚠️ 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.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
9.0
DANN
Benign
0.46
PhyloP100
0.92
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs1340787438; hg19: chr1-4772446; API