Variant 8-93734064-G-A 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_001377960.1(RBM12B):c.2347C>T(p.Pro783Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,584,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

RBM12B
NM_001377960.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RBM12B links:

RBM12B (HGNC:):

RBM12B 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=0.048337013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12B	NM_001377960.1 linkuse as main transcript	c.2347C>T	p.Pro783Ser	missense_variant	4/4	ENST00000520560.6	NP_001364889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM12B	ENST00000520560.6 linkuse as main transcript	c.2347C>T	p.Pro783Ser	missense_variant	4/4	2	NM_001377960.1	ENSP00000429807.2		Q8IXT5E5RHG1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000687

AC:

AN:

218388

Hom.:

AF XY:

0.0000754

AC XY:

AN XY:

119388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000543

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1432234

Hom.:

Cov.:

AF XY:

0.0000253

AC XY:

AN XY:

711392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000742

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:

0.00

Gnomad4 OTH exome

AF:

0.0000341

GnomAD4 genome

AF:

0.000217

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000212

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 27, 2024

The c.2347C>T (p.P783S) alteration is located in exon 3 (coding exon 1) of the RBM12B gene. This alteration results from a C to T substitution at nucleotide position 2347, causing the proline (P) at amino acid position 783 to be replaced by a serine (S). 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

-0.52

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0074

T;.;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.073

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.15

T;.;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.7

N;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.11

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.16

T;T;.

Sift4G

Benign

0.17

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.15

MutPred

0.34

Gain of phosphorylation at P783 (P = 2e-04);.;.;

MVP

0.59

ClinPred

0.13

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.15

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