Variant 5-98779973-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001366508.1(RGMB):c.530A>T(p.Asn177Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RGMB
NM_001366508.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

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/exons	MANE	UniProt
RGMB	NM_001366508.1 linkuse as main transcript	c.530A>T	p.Asn177Ile	missense_variant	2/3	ENST00000513185.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RGMB	ENST00000513185.3 linkuse as main transcript	c.530A>T	p.Asn177Ile	missense_variant	2/3	2	NM_001366508.1
RGMB	ENST00000308234.11 linkuse as main transcript	c.653A>T	p.Asn218Ile	missense_variant	4/5	1		P1
RGMB	ENST00000434027.2 linkuse as main transcript	n.1301A>T		non_coding_transcript_exon_variant	4/4	2
RGMB	ENST00000508978.1 linkuse as main transcript	n.129A>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Nov 08, 2022

The c.653A>T (p.N218I) alteration is located in exon 4 (coding exon 3) of the RGMB gene. This alteration results from a A to T substitution at nucleotide position 653, causing the asparagine (N) at amino acid position 218 to be replaced by an isoleucine (I). 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

0.16

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

.;D

Eigen

Benign

-0.15

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

0.073

MutationAssessor

Benign

0.34

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.31

Sift

Benign

0.11

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.061

.;B

Vest4

0.39

MutPred

0.33

.;Gain of helix (P = 0.062);

MVP

0.97

MPC

0.30

ClinPred

0.79

GERP RS

5.4

Varity_R

0.66

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over