chr12-56571806-C-T

Variant names:

• chr12-56571806-C-T
• rs144330252
• NM_002898.4:c.493C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002898.4(RBMS2):​c.493C>T​(p.Arg165Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000877 in 1,596,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: RBMS2 NM_002898.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.958
• Publications: 0 publications found

Genes affected

RBMS2 (HGNC:9909): (RNA binding motif single stranded interacting protein 2) The protein encoded by this gene is a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. The RBMS proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. This protein was isolated by phenotypic complementation of cdc2 and cdc13 mutants of yeast and is thought to suppress cdc2 and cdc13 mutants through the induction of translation of cdc2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS2	NM_002898.4	MANE Select	c.493C>T	p.Arg165Cys	missense	Exon 5 of 14	NP_002889.1	Q15434
	RBMS2	NM_001414460.1		c.493C>T	p.Arg165Cys	missense	Exon 5 of 13	NP_001401389.1
	RBMS2	NM_001414461.1		c.493C>T	p.Arg165Cys	missense	Exon 5 of 14	NP_001401390.1	Q15434

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS2	ENST00000262031.10	TSL:1 MANE Select	c.493C>T	p.Arg165Cys	missense	Exon 5 of 14	ENSP00000262031.5	Q15434
	RBMS2	ENST00000552916.5	TSL:1	n.*179C>T		non_coding_transcript_exon	Exon 4 of 12	ENSP00000450127.1	F8VQS9
	RBMS2	ENST00000552916.5	TSL:1	n.*179C>T		3_prime_UTR	Exon 4 of 12	ENSP00000450127.1	F8VQS9

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152076 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000835 AC: 2 AN: 239378 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000762 AC: 11 AN: 1444172 Hom.: 0 Cov.: 30 AF XY: 0.00000697 AC XY: 5 AN XY: 717264

African (AFR) AF: 0.00 AC: 0 AN: 32888

American (AMR) AF: 0.0000473 AC: 2 AN: 42266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38892

South Asian (SAS) AF: 0.0000238 AC: 2 AN: 83994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000545 AC: 6 AN: 1101922

Other (OTH) AF: 0.00 AC: 0 AN: 59608

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152076 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.96
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-7.6	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.42
MPC		1.2
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.86
gMVP		0.61
Mutation Taster		=26/74	disease causing

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: rs144330252; hg19: chr12-56965590;