20-35653359-G-A

Position:

chr20-35653359-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006047.6(RBM12):c.1964C>T(p.Ala655Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,096 control chromosomes in the GnomAD database, including 15 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

RBM12
NM_006047.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.938

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045345426).

BP6

Variant 20-35653359-G-A is Benign according to our data. Variant chr20-35653359-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 708628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 319 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6 linkuse as main transcript	c.1964C>T	p.Ala655Val	missense_variant	3/3	ENST00000374114.8	NP_006038.2	Q9NTZ6
CPNE1	NM_152925.3 linkuse as main transcript	c.-1+11401C>T		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.1964C>T	p.Ala655Val	missense_variant	3/3	1	NM_006047.6	ENSP00000363228.3	Q9NTZ6
CPNE1	ENST00000397443.7 linkuse as main transcript	c.-1+11401C>T		intron_variant		5	NM_152925.3	ENSP00000380585.1	Q99829
CPNE1	ENST00000437340.5 linkuse as main transcript	c.-1+11443C>T		intron_variant		1		ENSP00000415597.1	F2Z2V0
ENSG00000272897	ENST00000541176.2 linkuse as main transcript	n.*32+1843C>T		intron_variant		2		ENSP00000443983.2	H0YGN5

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

319

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00211

AC:

530

AN:

250964

Hom.:

AF XY:

0.00191

AC XY:

259

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00347

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00321

AC:

4689

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

2297

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00392

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00209

AC:

319

AN:

152312

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00287

Hom.:

Bravo

AF:

0.00238

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00200

AC:

243

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.68

.;.;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.19

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.079

MVP

0.26

MPC

0.21

ClinPred

0.0090

GERP RS

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.023

gMVP

0.40

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

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