20-35652813-G-T

Position:

chr20-35652813-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006047.6(RBM12):c.2510C>A(p.Pro837Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,604,394 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

RBM12
NM_006047.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.954

Variant links:

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]

RBM12 links:

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]

CPNE1 links:

ENSG00000272897 (HGNC:):

ENSG00000272897 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06166923).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6 linkuse as main transcript	c.2510C>A	p.Pro837Gln	missense_variant	3/3	ENST00000374114.8	NP_006038.2	Q9NTZ6
CPNE1	NM_152925.3 linkuse as main transcript	c.-1+11947C>A		intron_variant		ENST00000397443.7	NP_690902.1	Q99829

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RBM12	ENST00000374114.8 linkuse as main transcript	c.2510C>A	p.Pro837Gln	missense_variant	3/3	1	NM_006047.6	ENSP00000363228.3	Q9NTZ6
CPNE1	ENST00000397443.7 linkuse as main transcript	c.-1+11947C>A		intron_variant		5	NM_152925.3	ENSP00000380585.1	Q99829
CPNE1	ENST00000437340.5 linkuse as main transcript	c.-1+11989C>A		intron_variant		1		ENSP00000415597.1	F2Z2V0
ENSG00000272897	ENST00000541176.2 linkuse as main transcript	n.*32+2389C>A		intron_variant		2		ENSP00000443983.2	H0YGN5

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000684

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000298

AC:

AN:

234536

Hom.:

AF XY:

0.0000156

AC XY:

AN XY:

128208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1453226

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722554

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000185

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73856

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000684

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2022

The c.2510C>A (p.P837Q) alteration is located in exon 3 (coding exon 1) of the RBM12 gene. This alteration results from a C to A substitution at nucleotide position 2510, causing the proline (P) at amino acid position 837 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.061

T;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

.;.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.062

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.11

N;N;N

REVEL

Benign

0.026

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.089

B;B;B

Vest4

0.23

MutPred

0.27

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.24

MPC

0.19

ClinPred

0.050

GERP RS

4.2

Varity_R

0.087

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over