5-146230821-A-C

Variant names:

• chr5-146230821-A-C
• NM_018989.2:c.754A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018989.2(RBM27):​c.754A>C​(p.Thr252Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM27 NM_018989.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.32

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]

ENSG00000275740 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM27	NM_018989.2	c.754A>C	p.Thr252Pro	missense_variant	Exon 6 of 21	ENST00000265271.7	NP_061862.1
LOC127814297	NM_001414499.1	c.754A>C	p.Thr252Pro	missense_variant	Exon 6 of 20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7	c.754A>C	p.Thr252Pro	missense_variant	Exon 6 of 21	1	NM_018989.2	ENSP00000265271.5
ENSG00000275740	ENST00000506502.2	c.754A>C	p.Thr252Pro	missense_variant	Exon 6 of 20	5		ENSP00000475384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.754A>C (p.T252P) 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 754, causing the threonine (T) at amino acid position 252 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	0.28
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.3	.;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.054	T;D
Polyphen		1.0	.;D
Vest4		0.66
MutPred		0.089		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.44
MPC		0.98
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.62

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.

Other links and lift over

hg19: chr5-145610384;