Variant chr1-110339877-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022768.5(RBM15):c.472T>G(p.Ser158Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,602,942 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

RBM15
NM_022768.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

RBM15 (HGNC:14959): (RNA binding motif protein 15) Members of the SPEN (Split-end) family of proteins, including RBM15, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM, Feb 2009]

RBM15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023350924).

BS2

High AC in GnomAd4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM15	NM_022768.5 linkuse as main transcript	c.472T>G	p.Ser158Ala	missense_variant	1/3	ENST00000369784.9	NP_073605.4
RBM15	NM_001201545.2 linkuse as main transcript	c.472T>G	p.Ser158Ala	missense_variant	1/2		NP_001188474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM15	ENST00000369784.9 linkuse as main transcript	c.472T>G	p.Ser158Ala	missense_variant	1/3	1	NM_022768.5	ENSP00000358799	A2	Q96T37-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000456

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000186

AC:

AN:

247656

Hom.:

AF XY:

0.000201

AC XY:

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.0000641

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000404

AC:

586

AN:

1450794

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

279

AN XY:

719522

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000495

Gnomad4 OTH exome

AF:

0.000401

GnomAD4 genome

AF:

0.000237

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000358

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000189

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.472T>G (p.S158A) alteration is located in exon 1 (coding exon 1) of the RBM15 gene. This alteration results from a T to G substitution at nucleotide position 472, causing the serine (S) at amino acid position 158 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.20

T;.;.;T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.39

.;T;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.023

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

N;N;N;N;.

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.12

N;.;.;.;.

REVEL

Benign

0.013

Sift

Benign

0.21

T;.;.;.;.

Sift4G

Benign

0.85

T;T;T;T;T

Polyphen

0.023

B;.;B;B;.

Vest4

0.12

MVP

0.41

MPC

0.60

ClinPred

0.034

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.12

gMVP

0.21

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