Variant 12-113920688-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016196.4(RBM19):c.2308G>C(p.Val770Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,412 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RBM19
NM_016196.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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:

RBM19 (HGNC:):

RBM19 links:

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ACMG classification

Classification made for transcript

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=0.08665499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM19	NM_016196.4 linkuse as main transcript	c.2308G>C	p.Val770Leu	missense_variant, splice_region_variant	19/24	ENST00000261741.10	NP_057280.2	Q9Y4C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM19	ENST00000261741.10 linkuse as main transcript	c.2308G>C	p.Val770Leu	missense_variant, splice_region_variant	19/24	1	NM_016196.4	ENSP00000261741.5	Q9Y4C8
RBM19	ENST00000392561.7 linkuse as main transcript	c.2308G>C	p.Val770Leu	missense_variant, splice_region_variant	19/25	1		ENSP00000376344.3	Q9Y4C8
RBM19	ENST00000545145.6 linkuse as main transcript	c.2308G>C	p.Val770Leu	missense_variant, splice_region_variant	19/25	2		ENSP00000442053.2	Q9Y4C8
RBM19	ENST00000552386.1 linkuse as main transcript	n.442G>C		splice_region_variant, non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251456

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461412

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Sep 08, 2024

The c.2308G>C (p.V770L) alteration is located in exon 19 (coding exon 19) of the RBM19 gene. This alteration results from a G to C substitution at nucleotide position 2308, causing the valine (V) at amino acid position 770 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.040

T;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.76

.;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.24

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.54

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.011

B;B;B

Vest4

0.17

MutPred

0.34

Gain of catalytic residue at S773 (P = 0.0021);Gain of catalytic residue at S773 (P = 0.0021);Gain of catalytic residue at S773 (P = 0.0021);

MVP

0.16

MPC

0.13

ClinPred

0.093

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.22

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