Variant chr1-110339478-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022768.5(RBM15):c.73A>G(p.Thr25Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T25R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RBM15
NM_022768.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08639562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM15	NM_022768.5 linkuse as main transcript	c.73A>G	p.Thr25Ala	missense_variant	1/3	ENST00000369784.9
RBM15	NM_001201545.2 linkuse as main transcript	c.73A>G	p.Thr25Ala	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM15	ENST00000369784.9 linkuse as main transcript	c.73A>G	p.Thr25Ala	missense_variant	1/3	1	NM_022768.5	A2	Q96T37-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1418136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 05, 2023

The c.73A>G (p.T25A) alteration is located in exon 1 (coding exon 1) of the RBM15 gene. This alteration results from a A to G substitution at nucleotide position 73, causing the threonine (T) at amino acid position 25 to be replaced by an alanine (A). 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

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.19

T;.;.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.56

.;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.086

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L;L;L

MutationTaster

Benign

0.96

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.45

N;.;.;.

REVEL

Benign

0.035

Sift

Benign

0.13

T;.;.;.

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.023

B;.;B;B

Vest4

0.16

MutPred

0.14

Loss of phosphorylation at T25 (P = 0.0418);Loss of phosphorylation at T25 (P = 0.0418);Loss of phosphorylation at T25 (P = 0.0418);Loss of phosphorylation at T25 (P = 0.0418);

MVP

0.39

MPC

0.91

ClinPred

0.39

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.093

gMVP

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over