5-98774155-C-T

Variant names:

• chr5-98774155-C-T
• rs926058865
• NM_001366508.1:c.85C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366508.1(RGMB):​c.85C>T​(p.Pro29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,345,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. P29T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RGMB NM_001366508.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2615272).

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.85C>T	p.Pro29Ser	missense	Exon 1 of 3	NP_001353437.1	Q6NW40
	RGMB	NM_001012761.3		c.208C>T	p.Pro70Ser	missense	Exon 3 of 5	NP_001012779.2	J3KNF6
	RGMB	NM_001366509.1		c.208C>T	p.Pro70Ser	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.85C>T	p.Pro29Ser	missense	Exon 1 of 3	ENSP00000423256.1	Q6NW40
	RGMB	ENST00000308234.11	TSL:1	c.208C>T	p.Pro70Ser	missense	Exon 3 of 5	ENSP00000308219.7	J3KNF6
	RGMB	ENST00000894564.1		c.85C>T	p.Pro29Ser	missense	Exon 5 of 7	ENSP00000564623.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1345702 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663670

African (AFR) AF: 0.00 AC: 0 AN: 27430

American (AMR) AF: 0.00 AC: 0 AN: 32110

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 31266

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4056

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1062044

Other (OTH) AF: 0.00 AC: 0 AN: 56208

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.63	N
PhyloP100		0.62
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.23
Sift	Benign	0.23	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.38		Loss of glycosylation at P29 (P = 0.0217)
MVP		0.60
MPC		0.25
ClinPred		0.13	T
GERP RS		3.3
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.035
gMVP		0.52
Mutation Taster		=88/12	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: rs926058865; hg19: chr5-98109859;