Variant 7-155711335-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_053043.3(RBM33):c.1081A>C(p.Met361Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,604,374 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00090 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

RBM33
NM_053043.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.620

Variant links:

Genes affected

RBM33 (HGNC:27223): (RNA binding motif protein 33) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

RBM33 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=0.010789126).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3 linkuse as main transcript	c.1081A>C	p.Met361Leu	missense_variant	8/18	ENST00000401878.8	NP_444271.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8 linkuse as main transcript	c.1081A>C	p.Met361Leu	missense_variant	8/18	5	NM_053043.3	ENSP00000384160	P3	Q96EV2-1

Frequencies

GnomAD3 genomes

AF:

0.000902

AC:

137

AN:

151904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00168

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000913

AC:

217

AN:

237620

Hom.:

AF XY:

0.000897

AC XY:

116

AN XY:

129370

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000936

Gnomad NFE exome

AF:

0.00170

Gnomad OTH exome

AF:

0.000718

GnomAD4 exome

AF:

0.00139

AC:

2018

AN:

1452352

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

996

AN XY:

722334

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000750

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.000901

AC:

137

AN:

152022

Hom.:

Cov.:

AF XY:

0.000834

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00168

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000744

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000478

AC:

ESP6500EA

AF:

0.000948

AC:

ExAC

AF:

0.00105

AC:

127

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

May 26, 2022

The c.1081A>C (p.M361L) alteration is located in exon 8 (coding exon 8) of the RBM33 gene. This alteration results from a A to C substitution at nucleotide position 1081, causing the methionine (M) at amino acid position 361 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

0.094

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.053

Sift

Benign

0.11

T;T

Sift4G

Benign

0.88

T;T

Polyphen

0.0

B;.

Vest4

0.21

MutPred

0.15

Gain of catalytic residue at M361 (P = 0.0638);.;

MVP

0.48

MPC

0.18

ClinPred

0.011

GERP RS

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.028

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