20-35652790-CA-C

Variant names:

• chr20-35652790-CA-C
• rs1262969313
• NM_006047.6:c.2532delT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_006047.6(RBM12):​c.2532delT​(p.Gly845AlafsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBM12 NM_006047.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.865
• Publications: 3 publications found

Genes affected

RBM12 (HGNC:9898): (RNA binding motif protein 12) This gene encodes a protein that contains several RNA-binding motifs, potential transmembrane domains, and proline-rich regions. This gene and the gene for copine I overlap at map location 20q11.21. Alternative splicing in the 5' UTR results in four transcript variants. All variants encode the same protein. [provided by RefSeq, Nov 2010]

CPNE1 (HGNC:2314): (copine 1) Calcium-dependent membrane-binding proteins may regulate molecular events at the interface of the cell membrane and cytoplasm. This gene encodes a calcium-dependent protein that also contains two N-terminal type II C2 domains and an integrin A domain-like sequence in the C-terminus. However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Alternate splicing results in multiple transcript variants encoding different proteins. [provided by RefSeq, Aug 2008]

ENSG00000272897 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0954 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-35652790-CA-C is Pathogenic according to our data. Variant chr20-35652790-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 433196.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006047.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM12	NM_006047.6	MANE Select	c.2532delT	p.Gly845AlafsTer13	frameshift	Exon 3 of 3	NP_006038.2
	CPNE1	NM_152925.3	MANE Select	c.-1+11969delT		intron	N/A	NP_690902.1
	RBM12	NM_001198838.2		c.2532delT	p.Gly845AlafsTer13	frameshift	Exon 3 of 3	NP_001185767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM12	ENST00000374114.8	TSL:1 MANE Select	c.2532delT	p.Gly845AlafsTer13	frameshift	Exon 3 of 3	ENSP00000363228.3
	RBM12	ENST00000359646.1	TSL:1	c.2532delT	p.Gly845AlafsTer13	frameshift	Exon 2 of 2	ENSP00000352668.1
	RBM12	ENST00000374104.7	TSL:1	c.2532delT	p.Gly845AlafsTer13	frameshift	Exon 3 of 3	ENSP00000363217.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457358 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724732

African (AFR) AF: 0.00 AC: 0 AN: 33242

American (AMR) AF: 0.00 AC: 0 AN: 44174

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85818

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109570

Other (OTH) AF: 0.00 AC: 0 AN: 60158

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Schizophrenia 19 Pathogenic:1

Aug 17, 2017

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.86
Mutation Taster		=2/198	disease causing (ClinVar)

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: rs1262969313; hg19: chr20-34240712;