15-93052418-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020211.3(RGMA):c.220G>A(p.Glu74Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000488 in 1,597,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
RGMA
NM_020211.3 missense
NM_020211.3 missense
Scores
4
8
4
Clinical Significance
Conservation
PhyloP100: 3.77
Genes affected
RGMA (HGNC:30308): (repulsive guidance molecule BMP co-receptor a) This gene encodes a member of the repulsive guidance molecule family. The encoded protein is a glycosylphosphatidylinositol-anchored glycoprotein that functions as an axon guidance protein in the developing and adult central nervous system. This protein may also function as a tumor suppressor in some cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RGMA | NM_020211.3 | c.220G>A | p.Glu74Lys | missense_variant | 3/4 | ENST00000329082.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RGMA | ENST00000329082.12 | c.220G>A | p.Glu74Lys | missense_variant | 3/4 | 1 | NM_020211.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152210Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000437 AC: 10AN: 229074Hom.: 0 AF XY: 0.0000552 AC XY: 7AN XY: 126706
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GnomAD4 exome AF: 0.0000485 AC: 70AN: 1444776Hom.: 0 Cov.: 32 AF XY: 0.0000501 AC XY: 36AN XY: 718688
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74484
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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 submitter | clinical testing | Ambry Genetics | Mar 06, 2023 | The c.244G>A (p.E82K) alteration is located in exon 3 (coding exon 3) of the RGMA gene. This alteration results from a G to A substitution at nucleotide position 244, causing the glutamic acid (E) at amino acid position 82 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Pathogenic
Sift
Benign
T;T;T;T;T;D
Sift4G
Benign
T;T;T;T;T;T
Vest4
MutPred
Gain of methylation at E74 (P = 0.0056);.;.;.;.;.;
MVP
MPC
0.70
ClinPred
D
GERP RS
gMVP
Splicing
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Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at