Variant 20-57391643-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017495.6(RBM38):c.62C>T(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000556 in 1,477,772 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

RBM38
NM_017495.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

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:40725): (RBM38 antisense RNA 1)

RBM38-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004431993).

BP6

Variant 20-57391643-C-T is Benign according to our data. Variant chr20-57391643-C-T is described in ClinVar as [Benign]. Clinvar id is 789858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM38	NM_017495.6 linkuse as main transcript	c.62C>T	p.Pro21Leu	missense_variant	1/4	ENST00000356208.10	NP_059965.2
RBM38-AS1	NR_149006.1 linkuse as main transcript	n.778+636G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM38	ENST00000356208.10 linkuse as main transcript	c.62C>T	p.Pro21Leu	missense_variant	1/4	1	NM_017495.6	ENSP00000348538	P1	Q9H0Z9-1
RBM38-AS1	ENST00000686390.1 linkuse as main transcript	n.470+636G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

439

AN:

150386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00194

GnomAD3 exomes

AF:

0.000396

AC:

AN:

108560

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

59610

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.000547

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:

0.00

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000288

AC:

382

AN:

1327278

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

168

AN XY:

654910

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000764

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000673

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00292

AC:

439

AN:

150494

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

222

AN XY:

73518

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.00106

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00192

Alfa

AF:

0.000972

Hom.:

ESP6500AA

AF:

0.00589

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000335

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0057

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.95

N;N

REVEL

Benign

0.053

Sift

Benign

0.15

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0030

B;.

Vest4

0.068

MVP

0.24

MPC

1.1

ClinPred

0.0081

GERP RS

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.075

gMVP

0.18

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