2-218270044-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001087.5(AAMP):ā€‹c.43C>Gā€‹(p.Pro15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

AAMP
NM_001087.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.02
Variant links:
Genes affected
AAMP (HGNC:18): (angio associated migratory cell protein) The gene is a member of the immunoglobulin superfamily. The encoded protein is associated with angiogenesis, with potential roles in endothelial tube formation and the migration of endothelial cells. It may also regulate smooth muscle cell migration via the RhoA pathway. The encoded protein can bind to heparin and may mediate heparin-sensitive cell adhesion. [provided by RefSeq, Oct 2014]
PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08723098).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AAMPNM_001087.5 linkc.43C>G p.Pro15Ala missense_variant Exon 1 of 11 ENST00000248450.9 NP_001078.2 Q13685
AAMPNM_001302545.2 linkc.43C>G p.Pro15Ala missense_variant Exon 1 of 11 NP_001289474.1 C9JEH3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AAMPENST00000248450.9 linkc.43C>G p.Pro15Ala missense_variant Exon 1 of 11 1 NM_001087.5 ENSP00000248450.4 Q13685

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251188
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461816
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
23
DANN
Benign
0.84
DEOGEN2
Benign
0.025
T;T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.087
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.087
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.045
Sift
Benign
0.19
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0070
B;B
Vest4
0.34
MVP
0.44
MPC
0.56
ClinPred
0.084
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145888617; hg19: chr2-219134767; API