rs759631593

Variant names:

• chr5-146229790-C-G
• rs759631593
• NM_018989.2:c.469C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-146229790-C-G
• chr5-146229790-C-T

Variant summary

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

The NM_018989.2(RBM27):​c.469C>G​(p.Arg157Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,462 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. R157C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBM27 NM_018989.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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.469C>G	p.Arg157Gly	missense_variant	Exon 5 of 21	ENST00000265271.7	NP_061862.1
LOC127814297	NM_001414499.1	c.469C>G	p.Arg157Gly	missense_variant	Exon 5 of 20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7	c.469C>G	p.Arg157Gly	missense_variant	Exon 5 of 21	1	NM_018989.2	ENSP00000265271.5
ENSG00000275740	ENST00000506502.2	c.469C>G	p.Arg157Gly	missense_variant	Exon 5 of 20	5		ENSP00000475384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 246638 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134274

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461462 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727026

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000830 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.0010	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.0	.;D
REVEL	Benign	0.18
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	.;D
Vest4		0.60
MutPred		0.29		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.67
MPC		0.88
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.55
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs759631593; hg19: chr5-145609353;