chr20-35653261-G-A

Position:

• chr20-35653261-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006047.6(RBM12):​c.2062C>T​(p.Pro688Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM12 NM_006047.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2256077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12	NM_006047.6	c.2062C>T	p.Pro688Ser	missense_variant	3/3	ENST00000374114.8	NP_006038.2
CPNE1	NM_152925.3	c.-1+11499C>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.2062C>T	p.Pro688Ser	missense_variant	3/3	1	NM_006047.6	ENSP00000363228.3
CPNE1	ENST00000397443.7	c.-1+11499C>T		intron_variant		5	NM_152925.3	ENSP00000380585.1
CPNE1	ENST00000437340.5	c.-1+11541C>T		intron_variant		1		ENSP00000415597.1
ENSG00000272897	ENST00000541176.2	n.*32+1941C>T		intron_variant		2		ENSP00000443983.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1460942 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726800

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.2062C>T (p.P688S) alteration is located in exon 3 (coding exon 1) of the RBM12 gene. This alteration results from a C to T substitution at nucleotide position 2062, causing the proline (P) at amino acid position 688 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T;T;T
Eigen	Benign	0.080
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	.;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.024	D;D;D
Sift4G	Benign	0.43	T;T;T
Polyphen		0.96	D;D;D
Vest4		0.32
MutPred		0.26		Gain of glycosylation at P688 (P = 0.011);Gain of glycosylation at P688 (P = 0.011);Gain of glycosylation at P688 (P = 0.011);
MVP		0.32
MPC		0.68
ClinPred		0.74	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.42

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: rs1284027305; hg19: chr20-34241183;