Variant chr5-146229847-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018989.2(RBM27):c.526C>G(p.Leu176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,461,750 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RBM27
NM_018989.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07760355).

BS2

High AC in GnomAdExome4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM27	NM_018989.2 link	c.526C>G	p.Leu176Val	missense_variant	5/21	ENST00000265271.7	NP_061862.1	Q9P2N5
LOC127814297	NM_001414499.1 link	c.526C>G	p.Leu176Val	missense_variant	5/20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7 link	c.526C>G	p.Leu176Val	missense_variant	5/21	1	NM_018989.2	ENSP00000265271.5		Q9P2N5
ENSG00000275740	ENST00000506502.2 link	c.526C>G	p.Leu176Val	missense_variant	5/20	5		ENSP00000475384.1		U3KPZ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

246590

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000453

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000249

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

Apr 12, 2022

The c.526C>G (p.L176V) alteration is located in exon 5 (coding exon 5) of the RBM27 gene. This alteration results from a C to G substitution at nucleotide position 526, causing the leucine (L) at amino acid position 176 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.80

T;D

M_CAP

Benign

0.0067

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.85

.;N

REVEL

Benign

0.044

Sift

Benign

0.24

.;T

Sift4G

Benign

0.50

T;T

Polyphen

0.79

.;P

Vest4

0.22

MutPred

0.20

Gain of methylation at K172 (P = 0.1006);Gain of methylation at K172 (P = 0.1006);

MVP

0.20

MPC

0.34

ClinPred

0.043

GERP RS

2.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.043

gMVP

0.24

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