Variant chr20-57391604-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000356208.10(RBM38):c.23G>A(p.Cys8Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,392,208 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

RBM38
ENST00000356208.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

Variant links:

Genes affected

RBM38 (HGNC:15818): (RNA binding motif protein 38) Enables mRNA 3'-UTR binding activity. Involved in DNA damage response, signal transduction by p53 class mediator; negative regulation of cell population proliferation; and regulation of RNA metabolic process. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RBM38 links:

RBM38-AS1 (HGNC:):

RBM38-AS1 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=0.0061603487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM38	NM_017495.6 linkuse as main transcript	c.23G>A	p.Cys8Tyr	missense_variant	1/4	ENST00000356208.10	NP_059965.2	Q9H0Z9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM38	ENST00000356208.10 linkuse as main transcript	c.23G>A	p.Cys8Tyr	missense_variant	1/4	1	NM_017495.6	ENSP00000348538.5		Q9H0Z9-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

149392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000666

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00760

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000392

AC:

AN:

74036

Hom.:

AF XY:

0.000399

AC XY:

AN XY:

42592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000104

Gnomad ASJ exome

AF:

0.000186

Gnomad EAS exome

AF:

0.00791

Gnomad SAS exome

AF:

0.000872

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.000553

GnomAD4 exome

AF:

0.000181

AC:

225

AN:

1242706

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

118

AN XY:

612948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000549

Gnomad4 ASJ exome

AF:

0.000573

Gnomad4 EAS exome

AF:

0.00549

Gnomad4 SAS exome

AF:

0.000644

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.000451

GnomAD4 genome

AF:

0.000381

AC:

AN:

149502

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

AN XY:

72996

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000665

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00763

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000146

Hom.:

Bravo

AF:

0.000314

ExAC

AF:

0.000334

AC:

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

Dec 28, 2022

The c.23G>A (p.C8Y) alteration is located in exon 1 (coding exon 1) of the RBM38 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the cysteine (C) at amino acid position 8 to be replaced by a tyrosine (Y). 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

0.35

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0064

T;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.59

T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

0.95

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.040

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.042

D;T

Polyphen

0.052

B;.

Vest4

0.26

MVP

0.24

MPC

1.8

ClinPred

0.060

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.21

gMVP

0.33

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