12-113823265-C-G

Variant names:

• chr12-113823265-C-G
• NM_016196.4:c.2842G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016196.4(RBM19):​c.2842G>C​(p.Gly948Arg) 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. 14/21 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: RBM19 NM_016196.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062351137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM19	NM_016196.4	c.2842G>C	p.Gly948Arg	missense_variant	Exon 24 of 24	ENST00000261741.10	NP_057280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM19	ENST00000261741.10	c.2842G>C	p.Gly948Arg	missense_variant	Exon 24 of 24	1	NM_016196.4	ENSP00000261741.5
RBM19	ENST00000392561.7	c.2842G>C	p.Gly948Arg	missense_variant	Exon 24 of 25	1		ENSP00000376344.3
RBM19	ENST00000545145.6	c.2842G>C	p.Gly948Arg	missense_variant	Exon 24 of 25	2		ENSP00000442053.2
RBM19	ENST00000552384.1	n.292G>C		non_coding_transcript_exon_variant	Exon 3 of 4	3		ENSP00000449604.1

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

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2842G>C (p.G948R) alteration is located in exon 24 (coding exon 24) of the RBM19 gene. This alteration results from a G to C substitution at nucleotide position 2842, causing the glycine (G) at amino acid position 948 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	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T;T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	.;.;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.072
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.28
MutPred		0.27		Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);
MVP		0.26
MPC		0.16
ClinPred		0.35	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-114261070;