NM_016196.4:c.2282T>A

Variant names:

• chr12-113924720-A-T
• NM_016196.4:c.2282T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016196.4(RBM19):​c.2282T>A​(p.Ile761Asn) 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: 5.76
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016196.4. 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
	RBM19	NM_016196.4	MANE Select	c.2282T>A	p.Ile761Asn	missense	Exon 18 of 24	NP_057280.2	Q9Y4C8
	RBM19	NM_001146698.2		c.2282T>A	p.Ile761Asn	missense	Exon 18 of 25	NP_001140170.1	Q9Y4C8
	RBM19	NM_001146699.2		c.2282T>A	p.Ile761Asn	missense	Exon 18 of 25	NP_001140171.1	Q9Y4C8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM19	ENST00000261741.10	TSL:1 MANE Select	c.2282T>A	p.Ile761Asn	missense	Exon 18 of 24	ENSP00000261741.5	Q9Y4C8
	RBM19	ENST00000392561.7	TSL:1	c.2282T>A	p.Ile761Asn	missense	Exon 18 of 25	ENSP00000376344.3	Q9Y4C8
	RBM19	ENST00000970408.1		c.2282T>A	p.Ile761Asn	missense	Exon 18 of 27	ENSP00000640467.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		5.8
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.70		Loss of sheet (P = 0.007)
MVP		0.45
MPC		0.78
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.84
gMVP		0.82
Mutation Taster		=63/37	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

hg19: chr12-114362525;