15-93052174-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020211.3(RGMA):c.464C>T(p.Ser155Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,460,530 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
RGMA
NM_020211.3 missense
NM_020211.3 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 4.50
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RGMA | NM_020211.3 | c.464C>T | p.Ser155Leu | missense_variant | 3/4 | ENST00000329082.12 | NP_064596.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RGMA | ENST00000329082.12 | c.464C>T | p.Ser155Leu | missense_variant | 3/4 | 1 | NM_020211.3 | ENSP00000330005 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248438Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134944
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460530Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 726332
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GnomAD4 genome Cov.: 33
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33
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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 | Apr 27, 2022 | The c.488C>T (p.S163L) alteration is located in exon 3 (coding exon 3) of the RGMA gene. This alteration results from a C to T substitution at nucleotide position 488, causing the serine (S) at amino acid position 163 to be replaced by a leucine (L). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D;D;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Vest4
MutPred
Loss of disorder (P = 0.0312);.;.;.;.;.;
MVP
MPC
0.26
ClinPred
D
GERP RS
gMVP
Splicing
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Calibrated prediction
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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