12-113927113-C-G

Position:

• chr12-113927113-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016196.4(RBM19):​c.2185G>C​(p.Gly729Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RBM19 NM_016196.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

Genes affected

RBM19 (HGNC:29098): (RNA binding motif protein 19) This gene encodes a nucleolar protein that contains six RNA-binding motifs. The encoded protein may be involved in regulating ribosome biogenesis. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Apr 2009]

RBM19 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM19	NM_016196.4	c.2185G>C	p.Gly729Arg	missense_variant	17/24	ENST00000261741.10	NP_057280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM19	ENST00000261741.10	c.2185G>C	p.Gly729Arg	missense_variant	17/24	1	NM_016196.4	ENSP00000261741.5
RBM19	ENST00000392561.7	c.2185G>C	p.Gly729Arg	missense_variant	17/25	1		ENSP00000376344.3
RBM19	ENST00000545145.6	c.2185G>C	p.Gly729Arg	missense_variant	17/25	2		ENSP00000442053.2
RBM19	ENST00000552386.1	n.319G>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jan 31, 2024

The c.2185G>C (p.G729R) alteration is located in exon 17 (coding exon 17) of the RBM19 gene. This alteration results from a G to C substitution at nucleotide position 2185, causing the glycine (G) at amino acid position 729 to be replaced by an arginine (R). 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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.97	D;D;D
Vest4		0.88
MutPred		0.32		Gain of solvent accessibility (P = 0.0789);Gain of solvent accessibility (P = 0.0789);Gain of solvent accessibility (P = 0.0789);
MVP		0.91
MPC		0.60
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.71

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: chr12-114364918;