Genetic Variant RBM27:p.Pro334Thr (chr5-146233599-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018989.2(RBM27):c.1000C>A(p.Pro334Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,604 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P334S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RBM27
NM_018989.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.03

Publications

0 publications found

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:58349):

ENSG00000275740 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018989.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM27	NM_018989.2	MANE Select	c.1000C>A	p.Pro334Thr	missense	Exon 7 of 21	NP_061862.1	Q9P2N5
	RBM27-POU4F3	NM_001414499.1		c.1000C>A	p.Pro334Thr	missense	Exon 7 of 20	NP_001401428.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM27	ENST00000265271.7	TSL:1 MANE Select	c.1000C>A	p.Pro334Thr	missense	Exon 7 of 21	ENSP00000265271.5	Q9P2N5
ENSG00000275740	ENST00000506502.2	TSL:5	c.1000C>A	p.Pro334Thr	missense	Exon 7 of 20	ENSP00000475384.1	U3KPZ7
RBM27	ENST00000861565.1		c.1003C>A	p.Pro335Thr	missense	Exon 7 of 21	ENSP00000531624.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248722

AF XY:

0.00000740

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459604

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110234

Other (OTH)

AF:

0.00

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

5.0

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.12

Sift

Uncertain

0.014

Sift4G

Uncertain

0.041

Polyphen

0.73

Vest4

0.72

MutPred

0.41

Gain of phosphorylation at P334 (P = 0.0084)

MVP

0.36

MPC

0.62

ClinPred

0.62

GERP RS

5.6

Varity_R

0.30

gMVP

0.62

Mutation Taster

=67/33

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over