Variant 2-237818063-A-T 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.1144A>T(p.Thr382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,918 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

RBM44
NM_001080504.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.709

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:

Genome browser will be placed here

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=0.014579177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM44	NM_001080504.3 linkuse as main transcript	c.1144A>T	p.Thr382Ser	missense_variant	3/16	ENST00000316997.9	NP_001073973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RBM44	ENST00000316997.9 linkuse as main transcript	c.1144A>T	p.Thr382Ser	missense_variant	3/16	5	NM_001080504.3	ENSP00000321179	P1
RBM44	ENST00000409864.6 linkuse as main transcript	c.1144A>T	p.Thr382Ser	missense_variant	3/15	5		ENSP00000386727	P1
RBM44	ENST00000480583.5 linkuse as main transcript	n.1635A>T		non_coding_transcript_exon_variant	3/15	2
RBM44	ENST00000444524.2 linkuse as main transcript	n.202-2112A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152020

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

246624

Hom.:

AF XY:

0.0000597

AC XY:

AN XY:

133938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460778

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74370

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:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 06, 2024

The c.1147A>T (p.T383S) alteration is located in exon 3 (coding exon 2) of the RBM44 gene. This alteration results from a A to T substitution at nucleotide position 1147, causing the threonine (T) at amino acid position 383 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.56

DANN

Benign

0.71

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.31

T;.

M_CAP

Benign

0.0052

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.016

Sift

Benign

0.73

T;T

Sift4G

Benign

0.79

T;T

Vest4

0.090

MVP

0.12

MPC

0.020

ClinPred

0.011

GERP RS

-6.0

gMVP

0.044

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