Variant 12-113927218-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016196.4(RBM19):c.2080G>A(p.Glu694Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000289 in 1,559,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

RBM19
NM_016196.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.294

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.03733194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM19	NM_016196.4 linkuse as main transcript	c.2080G>A	p.Glu694Lys	missense_variant	17/24	ENST00000261741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RBM19	ENST00000261741.10 linkuse as main transcript	c.2080G>A	p.Glu694Lys	missense_variant	17/24	1	NM_016196.4	P1
RBM19	ENST00000392561.7 linkuse as main transcript	c.2080G>A	p.Glu694Lys	missense_variant	17/25	1		P1
RBM19	ENST00000545145.6 linkuse as main transcript	c.2080G>A	p.Glu694Lys	missense_variant	17/25	2		P1
RBM19	ENST00000552386.1 linkuse as main transcript	n.214G>A		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000734

AC:

AN:

163584

Hom.:

AF XY:

0.0000580

AC XY:

AN XY:

86208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000800

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.000258

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000427

GnomAD4 exome

AF:

0.0000277

AC:

AN:

1406990

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

694974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000627

Gnomad4 AMR exome

AF:

0.0000554

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000545

Gnomad4 SAS exome

AF:

0.000200

Gnomad4 FIN exome

AF:

0.000101

Gnomad4 NFE exome

AF:

0.00000646

Gnomad4 OTH exome

AF:

0.0000685

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000176

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.2080G>A (p.E694K) alteration is located in exon 17 (coding exon 17) of the RBM19 gene. This alteration results from a G to A substitution at nucleotide position 2080, causing the glutamic acid (E) at amino acid position 694 to be replaced by a lysine (K). 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

0.057

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.66

Cadd

Benign

6.0

Dann

Benign

0.88

DEOGEN2

Benign

0.056

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.0047

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.27

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.63

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.11

MutPred

0.37

Gain of ubiquitination at E694 (P = 0.0039);Gain of ubiquitination at E694 (P = 0.0039);Gain of ubiquitination at E694 (P = 0.0039);

MVP

0.12

MPC

0.14

ClinPred

0.0066

GERP RS

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over