Variant 20-57392736-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017495.6(RBM38):c.320A>G(p.Asn107Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RBM38
NM_017495.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.97

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM38	NM_017495.6 linkuse as main transcript	c.320A>G	p.Asn107Ser	missense_variant	2/4	ENST00000356208.10	NP_059965.2
RBM38-AS1	NR_149006.1 linkuse as main transcript	n.321T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM38	ENST00000356208.10 linkuse as main transcript	c.320A>G	p.Asn107Ser	missense_variant	2/4	1	NM_017495.6	ENSP00000348538	P1	Q9H0Z9-1
RBM38-AS1	ENST00000686390.1 linkuse as main transcript	n.13T>C		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248184

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135062

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460666

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726612

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jan 19, 2024

The c.320A>G (p.N107S) alteration is located in exon 2 (coding exon 2) of the RBM38 gene. This alteration results from a A to G substitution at nucleotide position 320, causing the asparagine (N) at amino acid position 107 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Benign

0.078

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.30

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.97

D;.;.

Vest4

0.75

MutPred

0.47

Gain of phosphorylation at Y110 (P = 0.1612);Gain of phosphorylation at Y110 (P = 0.1612);.;

MVP

0.75

MPC

2.0

ClinPred

0.98

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.92

gMVP

0.79

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