Variant 2-237817618-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080504.3(RBM44):c.699A>C(p.Glu233Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,612,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RBM44
NM_001080504.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.299

Variant links:

Genes affected

RBM44 (HGNC:24756): (RNA binding motif protein 44) Predicted to enable protein homodimerization activity. Predicted to be located in cytoplasm and intercellular bridge. [provided by Alliance of Genome Resources, Apr 2022]

RBM44 links:

RBM44 (HGNC:):

RBM44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.085069746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM44	NM_001080504.3 linkuse as main transcript	c.699A>C	p.Glu233Asp	missense_variant	3/16	ENST00000316997.9	NP_001073973.3	Q6ZP01Q8N7S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM44	ENST00000316997.9 linkuse as main transcript	c.699A>C	p.Glu233Asp	missense_variant	3/16	5	NM_001080504.3	ENSP00000321179.5	Q6ZP01
RBM44	ENST00000409864.6 linkuse as main transcript	c.699A>C	p.Glu233Asp	missense_variant	3/15	5		ENSP00000386727.2	Q6ZP01
RBM44	ENST00000480583.5 linkuse as main transcript	n.1190A>C		non_coding_transcript_exon_variant	3/15	2
RBM44	ENST00000444524.2 linkuse as main transcript	n.202-2557A>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000445

AC:

AN:

247444

Hom.:

AF XY:

0.0000521

AC XY:

AN XY:

134274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

224

AN:

1460768

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000118

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000270

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000497

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.702A>C (p.E234D) alteration is located in exon 3 (coding exon 2) of the RBM44 gene. This alteration results from a A to C substitution at nucleotide position 702, causing the glutamic acid (E) at amino acid position 234 to be replaced by an aspartic acid (D). 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

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.4

DANN

Uncertain

0.99

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.42

T;.

M_CAP

Benign

0.0027

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.059

Sift

Benign

0.17

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.13

MVP

0.34

MPC

0.022

ClinPred

0.037

GERP RS

0.093

gMVP

0.062

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over