Genetic Variant RBM33:p.Pro143Ser (chr7-155680768-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_053043.3(RBM33):c.427C>T(p.Pro143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,392 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

RBM33
NM_053043.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.245

Publications

1 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017271966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053043.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM33	NM_053043.3	MANE Select	c.427C>T	p.Pro143Ser	missense	Exon 5 of 18	NP_444271.2	Q96EV2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM33	ENST00000401878.8	TSL:5 MANE Select	c.427C>T	p.Pro143Ser	missense	Exon 5 of 18	ENSP00000384160.3	Q96EV2-1
RBM33	ENST00000440108.5	TSL:5	c.100C>T	p.Pro34Ser	missense	Exon 1 of 6	ENSP00000394987.1	H7C0H2
RBM33	ENST00000392759.7	TSL:5	c.427C>T	p.Pro143Ser	missense	Exon 5 of 7	ENSP00000376513.3	A8MTF7

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.0000242

AC:

AN:

248254

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000134

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1111736

Other (OTH)

AF:

0.000133

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000855

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41428

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67978

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.6

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.014

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.74

M_CAP

Benign

0.0063

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.050

PhyloP100

-0.24

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.1

REVEL

Benign

0.058

Sift

Benign

0.68

Sift4G

Benign

0.68

Polyphen

0.0080

Vest4

0.11

MVP

0.082

MPC

1.0

ClinPred

0.024

GERP RS

0.85

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.056

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over