Genetic Variant RBM45:p.Ile298Phe (chr2-178123560-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152945.4(RBM45):c.892A>T(p.Ile298Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,605,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RBM45
NM_152945.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19078448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM45	NM_152945.4 link	c.892A>T	p.Ile298Phe	missense_variant	Exon 6 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.892A>T	p.Ile298Phe	missense_variant	Exon 6 of 10	1	NM_152945.4	ENSP00000286070.5	Q8IUH3-3
RBM45	ENST00000424000.6 link	n.1015A>T		non_coding_transcript_exon_variant	Exon 6 of 9	2
RBM45	ENST00000493048.1 link	n.395A>T		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

242644

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1453318

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33014

American (AMR)

AF:

0.000117

AC:

AN:

42582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25658

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

84204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109362

Other (OTH)

AF:

0.0000166

AC:

AN:

60070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 08, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.892A>T (p.I298F) alteration is located in exon 6 (coding exon 6) of the RBM45 gene. This alteration results from a A to T substitution at nucleotide position 892, causing the isoleucine (I) at amino acid position 298 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0074

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

PhyloP100

1.2

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.070

Sift

Uncertain

0.014

.;D

Sift4G

Uncertain

0.032

D;D

Polyphen

0.0010

.;B

Vest4

0.38

MutPred

0.45

.;Gain of ubiquitination at K303 (P = 0.1222);

MVP

0.19

MPC

0.88

ClinPred

0.20

GERP RS

3.7

PromoterAI

0.021

Neutral

(source)

Varity_R

0.11

gMVP

0.60

Mutation Taster

=56/44

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.

chr2-178123560-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over