Genetic Variant NM_053043.3:c.630A>T (chr7-155700835-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_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. 16/22 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

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

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 rank	MANE	Protein	UniProt
RBM33	NM_053043.3 link	c.630A>T	p.Glu210Asp	missense_variant	Exon 6 of 18	ENST00000401878.8	NP_444271.2	Q96EV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8 link	c.630A>T	p.Glu210Asp	missense_variant	Exon 6 of 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

GnomAD2 exomes

AF:

0.000133

AC:

AN:

233676

AF XY:

0.000151

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 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

African (AFR)

AF:

0.00

AC:

AN:

33346

American (AMR)

AF:

0.000184

AC:

AN:

43554

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

25896

East Asian (EAS)

AF:

0.00

AC:

AN:

39530

South Asian (SAS)

AF:

0.000453

AC:

AN:

83882

European-Finnish (FIN)

AF:

0.0000754

AC:

AN:

53040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1106004

Other (OTH)

AF:

0.000166

AC:

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Oct 29, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.;.

PhyloP100

-0.12

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

PromoterAI

-0.0024

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.025

gMVP

0.021

Mutation Taster

=91/9

polymorphism

(source)

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

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NM_053043.3:c.630A>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over