Genetic Variant NM_018989.2:c.291A>T (chr5-146223515-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018989.2(RBM27):c.291A>T(p.Glu97Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBM27
NM_018989.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.30

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06399605).

BP6

Variant 5-146223515-A-T is Benign according to our data. Variant chr5-146223515-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3787553.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM27	NM_018989.2 link	c.291A>T	p.Glu97Asp	missense_variant	Exon 3 of 21	ENST00000265271.7	NP_061862.1	Q9P2N5
LOC127814297	NM_001414499.1 link	c.291A>T	p.Glu97Asp	missense_variant	Exon 3 of 20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7 link	c.291A>T	p.Glu97Asp	missense_variant	Exon 3 of 21	1	NM_018989.2	ENSP00000265271.5		Q9P2N5
ENSG00000275740	ENST00000506502.2 link	c.291A>T	p.Glu97Asp	missense_variant	Exon 3 of 20	5		ENSP00000475384.1		U3KPZ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1451250

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721728

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 22, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.034

.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.92

.;N

REVEL

Benign

0.094

Sift

Benign

0.58

.;T

Sift4G

Benign

0.27

T;T

Polyphen

0.45

.;B

Vest4

0.14

MutPred

0.17

Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);

MVP

0.22

MPC

0.29

ClinPred

0.28

GERP RS

3.5

Varity_R

0.061

gMVP

0.10

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