12-56522043-C-T

Variant names:

• chr12-56522043-C-T
• NM_002898.4:c.20C>T

Variant summary

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

The NM_002898.4(RBMS2):​c.20C>T​(p.Ser7Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RBMS2 NM_002898.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS2	NM_002898.4	c.20C>T	p.Ser7Phe	missense_variant	Exon 1 of 14	ENST00000262031.10	NP_002889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS2	ENST00000262031.10	c.20C>T	p.Ser7Phe	missense_variant	Exon 1 of 14	1	NM_002898.4	ENSP00000262031.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20C>T (p.S7F) alteration is located in exon 1 (coding exon 1) of the RBMS2 gene. This alteration results from a C to T substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by a phenylalanine (F). 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	Uncertain	0.38
BayesDel_addAF	Benign	0.00083	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0061	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.099
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.53	P;.
Vest4		0.60
MutPred		0.39		Loss of disorder (P = 0.0079);Loss of disorder (P = 0.0079);
MVP		0.35
MPC		0.47
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-56915827;