chr5-98779838-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001366508.1(RGMB):ā€‹c.395C>Gā€‹(p.Pro132Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000588 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000059 ( 0 hom. )

Consequence

RGMB
NM_001366508.1 missense

Scores

11
4
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67
Variant links:
Genes affected
RGMB (HGNC:26896): (repulsive guidance molecule BMP co-receptor b) RGMB is a glycosylphosphatidylinositol (GPI)-anchored member of the repulsive guidance molecule family (see RGMA, MIM 607362) and contributes to the patterning of the developing nervous system (Samad et al., 2005 [PubMed 15671031]).[supplied by OMIM, Apr 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.762
BS2
High AC in GnomAdExome4 at 86 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RGMBNM_001366508.1 linkuse as main transcriptc.395C>G p.Pro132Arg missense_variant 2/3 ENST00000513185.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RGMBENST00000513185.3 linkuse as main transcriptc.395C>G p.Pro132Arg missense_variant 2/32 NM_001366508.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000321
AC:
8
AN:
249170
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135198
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000708
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000588
AC:
86
AN:
1461702
Hom.:
0
Cov.:
32
AF XY:
0.0000509
AC XY:
37
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000684
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
Cov.:
33
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000248
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 GeneticsFeb 03, 2022The c.518C>G (p.P173R) alteration is located in exon 4 (coding exon 3) of the RGMB gene. This alteration results from a C to G substitution at nucleotide position 518, causing the proline (P) at amino acid position 173 to be replaced by an arginine (R). 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
0.15
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.81
.;D
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Benign
1.4
.;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.79
T
PROVEAN
Pathogenic
-6.8
D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
.;D
Vest4
0.59
MVP
0.98
MPC
0.90
ClinPred
0.86
D
GERP RS
5.4
Varity_R
0.78
gMVP
0.76

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: rs199764525; hg19: chr5-98115542; API