chr3-51391739-C-T

Variant names:

• chr3-51391739-C-T
• rs538902846
• NM_013286.5:c.340C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_013286.5(RBM15B):​c.340C>T​(p.Pro114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 1,532,860 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00054 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: RBM15B NM_013286.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

Genes affected

RBM15B (HGNC:24303): (RNA binding motif protein 15B) Members of the SPEN (Split-end) family of proteins, including RBM15B, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM, Feb 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004914254).
• BS2: High AC in GnomAd4 at 82 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013286.5. 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
	RBM15B	NM_013286.5	MANE Select	c.340C>T	p.Pro114Ser	missense	Exon 1 of 1	NP_037418.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM15B	ENST00000563281.2	TSL:6 MANE Select	c.340C>T	p.Pro114Ser	missense	Exon 1 of 1	ENSP00000454545.1	Q8NDT2-1

Frequencies

GnomAD3 genomes AF: 0.000540 AC: 82 AN: 151762 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000648

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000337 AC: 52 AN: 154240 AF XY: 0.000315

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000165

Gnomad ASJ exome AF: 0.000139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.000595

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000538 AC: 743 AN: 1380988 Hom.: 0 Cov.: 32 AF XY: 0.000544 AC XY: 373 AN XY: 685766

African (AFR) AF: 0.000141 AC: 4 AN: 28418

American (AMR) AF: 0.000169 AC: 6 AN: 35482

Ashkenazi Jewish (ASJ) AF: 0.0000419 AC: 1 AN: 23882

East Asian (EAS) AF: 0.0000307 AC: 1 AN: 32584

South Asian (SAS) AF: 0.000227 AC: 18 AN: 79254

European-Finnish (FIN) AF: 0.0000276 AC: 1 AN: 36252

Middle Eastern (MID) AF: 0.000210 AC: 1 AN: 4762

European-Non Finnish (NFE) AF: 0.000630 AC: 682 AN: 1083312

Other (OTH) AF: 0.000508 AC: 29 AN: 57042

GnomAD4 genome AF: 0.000540 AC: 82 AN: 151872 Hom.: 2 Cov.: 32 AF XY: 0.000633 AC XY: 47 AN XY: 74224

African (AFR) AF: 0.0000723 AC: 3 AN: 41510

American (AMR) AF: 0.000131 AC: 2 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000648 AC: 44 AN: 67850

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000624 Hom.: 0

Bravo AF: 0.000567

ExAC AF: 0.000330 AC: 37

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.030	N
Sift	Benign	0.25	T
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.18
MVP		0.10
ClinPred		0.030	T
GERP RS		2.8
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Varity_R		0.061
gMVP		0.31
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs538902846; hg19: chr3-51429170;