dbSNP rs766543405: RBM45:p.Pro280Arg (chr2-178121345-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152945.4(RBM45):c.839C>G(p.Pro280Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,401,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P280L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBM45
NM_152945.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

RBM45 (HGNC:24468): (RNA binding motif protein 45) This gene encodes a member of the RNA recognition motif (RRM)-type RNA-binding family of proteins. This protein exhibits preferential binding to poly(C) RNA. Initial cloning of this gene found that the rat ortholog was dynamically expressed in the developing rat brain. This protein has been localized to inclusion bodies in the brain and spinal cord of amyotrophic lateral sclerosis and Alzheimer's patients. A pseudogene has been identified on chromosome 8. [provided by RefSeq, Feb 2015]

RBM45 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM45	NM_152945.4 link	c.839C>G	p.Pro280Arg	missense_variant	Exon 5 of 10	ENST00000286070.10	NP_694453.2	Q8IUH3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM45	ENST00000286070.10 link	c.839C>G	p.Pro280Arg	missense_variant	Exon 5 of 10	1	NM_152945.4	ENSP00000286070.5	Q8IUH3-3
RBM45	ENST00000424000.6 link	n.962C>G		non_coding_transcript_exon_variant	Exon 5 of 9	2
RBM45	ENST00000493048.1 link	n.342C>G		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000484

AC:

AN:

206680

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000664

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1401136

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30282

American (AMR)

AF:

0.00

AC:

AN:

32084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23804

East Asian (EAS)

AF:

0.0000524

AC:

AN:

38154

South Asian (SAS)

AF:

0.00

AC:

AN:

75458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086354

Other (OTH)

AF:

0.00

AC:

AN:

57658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.072

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.0074

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.95

L;.

PhyloP100

3.6

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.54

.;N

REVEL

Benign

0.10

Sift

Benign

0.34

.;T

Sift4G

Benign

0.60

T;T

Polyphen

0.14

.;B

Vest4

0.74

MutPred

0.37

.;Gain of solvent accessibility (P = 0.0808);

MVP

0.34

MPC

0.67

ClinPred

0.24

GERP RS

5.1

Varity_R

0.24

gMVP

0.33

Mutation Taster

=76/24

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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rs766543405

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over