Genetic Variant RGMB:p.Pro28Leu (chr5-98774153-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366508.1(RGMB):c.83C>T(p.Pro28Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000002 in 1,498,052 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P28R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

RGMB
NM_001366508.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

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]

RGMB links:

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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 rank	MANE	Protein	UniProt
RGMB	NM_001366508.1 link	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 3	ENST00000513185.3	NP_001353437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RGMB	ENST00000513185.3 link	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 3	2	NM_001366508.1	ENSP00000423256.1	Q6NW40
RGMB	ENST00000308234.11 link	c.206C>T	p.Pro69Leu	missense_variant	Exon 3 of 5	1		ENSP00000308219.7	J3KNF6
RGMB	ENST00000434027.2 link	n.854C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
RGMB	ENST00000504776.5 link	n.487C>T		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000107

AC:

AN:

93564

Hom.:

AF XY:

0.0000190

AC XY:

AN XY:

52596

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:

0.0000539

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1345874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663774

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000422

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.42e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.64

T;T

M_CAP

Pathogenic

0.92

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Uncertain

0.085

MutationAssessor

Benign

0.90

.;L

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.46

Sift

Benign

0.11

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.85

.;P

Vest4

0.30

MutPred

0.62

.;Loss of glycosylation at P28 (P = 0.0025);

MVP

0.91

MPC

0.25

ClinPred

0.84

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.082

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over