Variant 7-155700835-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_053043.3(RBM33):c.630A>T(p.Glu210Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,603,402 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

RBM33
NM_053043.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.121

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01448825).

BP6

Variant 7-155700835-A-T is Benign according to our data. Variant chr7-155700835-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2393481.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3 linkuse as main transcript	c.630A>T	p.Glu210Asp	missense_variant	6/18	ENST00000401878.8	NP_444271.2	Q96EV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8 linkuse as main transcript	c.630A>T	p.Glu210Asp	missense_variant	6/18	5	NM_053043.3	ENSP00000384160.3		Q96EV2-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152170

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

233676

Hom.:

AF XY:

0.000151

AC XY:

AN XY:

125962

show subpopulations

Gnomad AFR exome

AF:

0.0000699

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.000310

Gnomad EAS exome

AF:

0.000118

Gnomad SAS exome

AF:

0.000428

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.0000477

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.0000620

AC:

AN:

1451116

Hom.:

Cov.:

AF XY:

0.0000735

AC XY:

AN XY:

720674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000184

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000453

Gnomad4 FIN exome

AF:

0.0000754

Gnomad4 NFE exome

AF:

0.0000235

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74468

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000265

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000108

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.4

DANN

Benign

0.86

DEOGEN2

Benign

0.021

.;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

0.59

N;N;N;N

REVEL

Benign

0.087

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.15

MutPred

0.056

Loss of stability (P = 0.2422);Loss of stability (P = 0.2422);.;.;

MVP

0.21

MPC

0.63

ClinPred

0.0066

GERP RS

-0.63

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.025

gMVP

0.021

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