15-93052114-G-C

Position:

• chr15-93052114-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020211.3(RGMA):​c.524C>G​(p.Thr175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RGMA NM_020211.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

Genes affected

RGMA (HGNC:30308): (repulsive guidance molecule BMP co-receptor a) This gene encodes a member of the repulsive guidance molecule family. The encoded protein is a glycosylphosphatidylinositol-anchored glycoprotein that functions as an axon guidance protein in the developing and adult central nervous system. This protein may also function as a tumor suppressor in some cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17872933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGMA	NM_020211.3	c.524C>G	p.Thr175Ser	missense_variant	3/4	ENST00000329082.12	NP_064596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGMA	ENST00000329082.12	c.524C>G	p.Thr175Ser	missense_variant	3/4	1	NM_020211.3	ENSP00000330005.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.548C>G (p.T183S) alteration is located in exon 3 (coding exon 3) of the RGMA gene. This alteration results from a C to G substitution at nucleotide position 548, causing the threonine (T) at amino acid position 183 to be replaced by a serine (S). 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	0.064
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.026	.;.;.;.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.59	.;.;.;.;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Uncertain	-0.19	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.34	N;N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.67	T;T;T;T;T;T
Sift4G	Benign	0.77	T;T;T;T;T;T
Vest4		0.23
MutPred		0.34		Gain of catalytic residue at T175 (P = 0.0501);.;.;.;.;.;
MVP		0.89
MPC		0.20
ClinPred		0.33	T
GERP RS		5.3
gMVP		0.39

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.

Other links and lift over

hg19: chr15-93595344;