5-98774122-G-T

Variant names:

• chr5-98774122-G-T
• rs1389589451
• NM_001366508.1:c.52G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366508.1(RGMB):​c.52G>T​(p.Glu18*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGMB NM_001366508.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• Publications: 0 publications found

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-AS1 (HGNC:48666): (RGMB antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGMB	NM_001366508.1	MANE Select	c.52G>T	p.Glu18*	stop_gained	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.175G>T	p.Glu59*	stop_gained	Exon 3 of 5	NP_001012779.2	J3KNF6
	RGMB	NM_001366509.1		c.175G>T	p.Glu59*	stop_gained	Exon 3 of 5	NP_001353438.1	J3KNF6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGMB	ENST00000513185.3	TSL:2 MANE Select	c.52G>T	p.Glu18*	stop_gained	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000308234.11	TSL:1	c.175G>T	p.Glu59*	stop_gained	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000894564.1		c.52G>T	p.Glu18*	stop_gained	Exon 5 of 7	ENSP00000564623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 98174 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1276154 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 633238

African (AFR) AF: 0.00 AC: 0 AN: 26096

American (AMR) AF: 0.00 AC: 0 AN: 32682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23492

East Asian (EAS) AF: 0.00 AC: 0 AN: 31094

South Asian (SAS) AF: 0.00 AC: 0 AN: 74628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 995324

Other (OTH) AF: 0.00 AC: 0 AN: 53920

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.32	N
PhyloP100		4.5
Vest4		0.76
GERP RS		4.0
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=10/190	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1389589451; hg19: chr5-98109826;