dbSNP rs139896702: RBM41:p.Val394Ile (chrX-107067661-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001324242.2(RBM41):c.1180G>A(p.Val394Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,207,658 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 149 hemizygotes in GnomAD. 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 0.00027 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00040 ( 0 hom. 143 hem. )

Consequence

RBM41
NM_001324242.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.573

Publications

2 publications found

Variant links:

Genes affected

RBM41 (HGNC:25617): (RNA binding motif protein 41) Predicted to enable U12 snRNA binding activity and pre-mRNA intronic binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

RBM41 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052877516).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324242.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM41	NM_001324242.2	MANE Select	c.1180G>A	p.Val394Ile	missense	Exon 8 of 8	NP_001311171.1	A0A8I5KYC8
RBM41	NM_001324243.1		c.1285G>A	p.Val429Ile	missense	Exon 8 of 8	NP_001311172.1
RBM41	NM_001394116.1		c.1231G>A	p.Val411Ile	missense	Exon 8 of 8	NP_001381045.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM41	ENST00000685964.1	MANE Select	c.1180G>A	p.Val394Ile	missense	Exon 8 of 8	ENSP00000509650.1	A0A8I5KYC8
RBM41	ENST00000372479.8	TSL:1	c.1108G>A	p.Val370Ile	missense	Exon 7 of 7	ENSP00000361557.3	Q96IZ5-1
RBM41	ENST00000965480.1		c.1264G>A	p.Val422Ile	missense	Exon 8 of 8	ENSP00000635539.1

Frequencies

GnomAD3 genomes

AF:

0.000268

AC:

AN:

111819

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000648

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:

0.000167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000509

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000199

AC:

AN:

181027

AF XY:

0.000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.000408

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000397

AC:

435

AN:

1095789

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

143

AN XY:

361473

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26337

American (AMR)

AF:

0.0000571

AC:

AN:

35007

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19283

East Asian (EAS)

AF:

0.00

AC:

AN:

30161

South Asian (SAS)

AF:

0.00

AC:

AN:

53564

European-Finnish (FIN)

AF:

0.000173

AC:

AN:

40418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4107

European-Non Finnish (NFE)

AF:

0.000498

AC:

419

AN:

840943

Other (OTH)

AF:

0.000131

AC:

AN:

45969

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000268

AC:

AN:

111869

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34091

show subpopulations

African (AFR)

AF:

0.0000647

AC:

AN:

30933

American (AMR)

AF:

0.00

AC:

AN:

10535

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3583

South Asian (SAS)

AF:

0.00

AC:

AN:

2689

European-Finnish (FIN)

AF:

0.000167

AC:

AN:

5998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000509

AC:

AN:

53059

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000437

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000198

AC:

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

0.080

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.15

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.81

M_CAP

Benign

0.0058

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

PhyloP100

0.57

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.70

REVEL

Benign

0.021

Sift

Benign

0.22

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.16

MVP

0.56

MPC

0.13

ClinPred

0.053

GERP RS

2.8

Varity_R

0.12

gMVP

0.32

Mutation Taster

=97/3

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