Variant chr2-237817495-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080504.3(RBM44):c.576A>C(p.Glu192Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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)

Consequence

RBM44
NM_001080504.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.469

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05725813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM44	NM_001080504.3 linkuse as main transcript	c.576A>C	p.Glu192Asp	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.576A>C	p.Glu192Asp	missense_variant	3/16	5	NM_001080504.3	ENSP00000321179.5	Q6ZP01
RBM44	ENST00000409864.6 linkuse as main transcript	c.576A>C	p.Glu192Asp	missense_variant	3/15	5		ENSP00000386727.2	Q6ZP01
RBM44	ENST00000480583.5 linkuse as main transcript	n.1067A>C		non_coding_transcript_exon_variant	3/15	2
RBM44	ENST00000444524.2 linkuse as main transcript	n.202-2680A>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000302

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

Jul 12, 2022

The c.579A>C (p.E193D) 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 579, causing the glutamic acid (E) at amino acid position 193 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.53

T;.

M_CAP

Benign

0.0024

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.032

Sift

Benign

0.074

T;T

Sift4G

Benign

0.14

T;T

Vest4

0.14

MVP

0.36

MPC

0.043

ClinPred

0.32

GERP RS

0.37

gMVP

0.094

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