Variant 5-146230660-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018989.2(RBM27):c.593A>C(p.His198Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBM27
NM_018989.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

RBM27 (HGNC:29243): (RNA binding motif protein 27) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be located in cytoplasm and nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RBM27 links:

ENSG00000275740 (HGNC:):

ENSG00000275740 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32237968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM27	NM_018989.2 link	c.593A>C	p.His198Pro	missense_variant	6/21	ENST00000265271.7	NP_061862.1	Q9P2N5
LOC127814297	NM_001414499.1 link	c.593A>C	p.His198Pro	missense_variant	6/20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7 link	c.593A>C	p.His198Pro	missense_variant	6/21	1	NM_018989.2	ENSP00000265271.5		Q9P2N5
ENSG00000275740	ENST00000506502.2 link	c.593A>C	p.His198Pro	missense_variant	6/20	5		ENSP00000475384.1		U3KPZ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248358

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000342

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727148

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 25, 2024

The c.593A>C (p.H198P) alteration is located in exon 6 (coding exon 6) of the RBM27 gene. This alteration results from a A to C substitution at nucleotide position 593, causing the histidine (H) at amino acid position 198 to be replaced by a proline (P). 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

0.26

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

.;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.6

.;L

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.4

.;N

REVEL

Benign

0.14

Sift

Uncertain

0.016

.;D

Sift4G

Benign

0.17

T;T

Polyphen

0.99

.;D

Vest4

0.57

MutPred

0.26

Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);

MVP

0.46

MPC

0.82

ClinPred

0.38

GERP RS

6.0

Varity_R

0.44

gMVP

0.42

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