2-218266579-C-G

Variant summary

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

The NM_001087.5(AAMP):ā€‹c.543G>Cā€‹(p.Glu181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

AAMP
NM_001087.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36
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]

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=0.246055).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AAMPNM_001087.5 linkuse as main transcriptc.543G>C p.Glu181Asp missense_variant 5/11 ENST00000248450.9 NP_001078.2
AAMPNM_001302545.2 linkuse as main transcriptc.546G>C p.Glu182Asp missense_variant 5/11 NP_001289474.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AAMPENST00000248450.9 linkuse as main transcriptc.543G>C p.Glu181Asp missense_variant 5/111 NM_001087.5 ENSP00000248450 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460722
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726572
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 01, 2024The c.543G>C (p.E181D) alteration is located in exon 5 (coding exon 5) of the AAMP gene. This alteration results from a G to C substitution at nucleotide position 543, causing the glutamic acid (E) at amino acid position 181 to be replaced by an aspartic acid (D). 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
Benign
0.19
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
T;T;.;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.054
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.25
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.68
N;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.97
N;N;N;N
REVEL
Benign
0.070
Sift
Benign
0.34
T;T;T;T
Sift4G
Benign
0.46
T;T;T;.
Polyphen
0.033
B;B;B;.
Vest4
0.50
MutPred
0.38
.;Loss of catalytic residue at E182 (P = 0.2107);.;.;
MVP
0.50
MPC
0.53
ClinPred
0.43
T
GERP RS
4.0
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.093
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219131302; API