rs781720548

Positions:

• chr20-35652946-C-A
• chr20-35652946-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_006047.6(RBM12):​c.2377G>T​(p.Gly793Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM12 NM_006047.6 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.09

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 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 0.151 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-35652946-C-A is Pathogenic according to our data. Variant chr20-35652946-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 433195.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6	c.2377G>T	p.Gly793Ter	stop_gained	3/3	ENST00000374114.8	NP_006038.2
CPNE1	NM_152925.3	c.-1+11814G>T		intron_variant		ENST00000397443.7	NP_690902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM12	ENST00000374114.8	c.2377G>T	p.Gly793Ter	stop_gained	3/3	1	NM_006047.6	ENSP00000363228	P1
CPNE1	ENST00000397443.7	c.-1+11814G>T		intron_variant		5	NM_152925.3	ENSP00000380585	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Schizophrenia 19 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 17, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.94	D
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
Vest4		0.28
GERP RS		5.9

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

LitVar

Other links and lift over

dbSNP: rs781720548; hg19: chr20-34240868;