NM_001366508.1:c.83C>G

Variant names:

• chr5-98774153-C-G
• rs1289615016
• NM_001366508.1:c.83C>G

Variant summary

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

The NM_001366508.1(RGMB):​c.83C>G​(p.Pro28Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000223 in 1,345,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: RGMB NM_001366508.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65
• 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.83C>G	p.Pro28Arg	missense	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.206C>G	p.Pro69Arg	missense	Exon 3 of 5	NP_001012779.2	J3KNF6
	RGMB	NM_001366509.1		c.206C>G	p.Pro69Arg	missense	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.83C>G	p.Pro28Arg	missense	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000308234.11	TSL:1	c.206C>G	p.Pro69Arg	missense	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000894564.1		c.83C>G	p.Pro28Arg	missense	Exon 5 of 7	ENSP00000564623.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000214 AC: 2 AN: 93564 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000995

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 AF: 0.00000223 AC: 3 AN: 1345874 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663774

African (AFR) AF: 0.00 AC: 0 AN: 27446

American (AMR) AF: 0.0000622 AC: 2 AN: 32168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23672

East Asian (EAS) AF: 0.00 AC: 0 AN: 31300

South Asian (SAS) AF: 0.00 AC: 0 AN: 75396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1062056

Other (OTH) AF: 0.00 AC: 0 AN: 56224

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Uncertain	0.050
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.016	D
Sift4G	Benign	0.30	T
Polyphen		0.82	P
Vest4		0.34
MutPred		0.56		Loss of glycosylation at P28 (P = 0.0025)
MVP		0.90
MPC		0.49
ClinPred		0.52	D
GERP RS		3.0
PromoterAI		0.020	Neutral
Varity_R		0.087
gMVP		0.34
Mutation Taster		=84/16	polymorphism

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: rs1289615016; hg19: chr5-98109857;