Variant 8-93733575-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001377960.1(RBM12B):c.2836C>T(p.His946Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00119 in 1,613,446 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

RBM12B
NM_001377960.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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:

ENSG00000253722 (HGNC:):

ENSG00000253722 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014020652).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM12B	NM_001377960.1 link	c.2836C>T	p.His946Tyr	missense_variant	Exon 4 of 4	ENST00000520560.6	NP_001364889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM12B	ENST00000520560.6 link	c.2836C>T	p.His946Tyr	missense_variant	Exon 4 of 4	2	NM_001377960.1	ENSP00000429807.2		Q8IXT5E5RHG1

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

113

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000682

AC:

170

AN:

249244

Hom.:

AF XY:

0.000628

AC XY:

AN XY:

135272

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000116

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:

0.00143

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00123

AC:

1801

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

877

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00157

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152214

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.000654

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00135

AC:

ExAC

AF:

0.000580

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00136

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 28, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2836C>T (p.H946Y) 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 2836, causing the histidine (H) at amino acid position 946 to be replaced by a tyrosine (Y). 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

0.15

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.019

T;.;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.84

T;.;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.0

N;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.21

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.60

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.062

B;.;.

Vest4

0.23

MVP

0.15

ClinPred

0.025

GERP RS

4.8

Varity_R

0.063

gMVP

0.67

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