14-73111002-T-C

Position:

• chr14-73111002-T-C

Variant summary

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

The NM_021239.3(RBM25):​c.1864T>C​(p.Ser622Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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)
• Consequence: RBM25 NM_021239.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

Genes affected

RBM25 (HGNC:23244): (RNA binding motif protein 25) Enables mRNA binding activity. Involved in regulation of alternative mRNA splicing, via spliceosome and regulation of apoptotic process. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18119797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM25	NM_021239.3	c.1864T>C	p.Ser622Pro	missense_variant	15/19	ENST00000261973.12	NP_067062.1
RBM25	XM_011537044.4	c.1864T>C	p.Ser622Pro	missense_variant	16/20		XP_011535346.1
RBM25	XM_047431641.1	c.1864T>C	p.Ser622Pro	missense_variant	15/16		XP_047287597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM25	ENST00000261973.12	c.1864T>C	p.Ser622Pro	missense_variant	15/19	1	NM_021239.3	ENSP00000261973	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 26, 2022

The c.1864T>C (p.S622P) alteration is located in exon 15 (coding exon 14) of the RBM25 gene. This alteration results from a T to C substitution at nucleotide position 1864, causing the serine (S) at amino acid position 622 to be replaced by a proline (P). 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	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	0.027
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.14
Sift	Benign	0.28	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.92	P;P
Vest4		0.36
MutPred		0.24		Gain of catalytic residue at S622 (P = 0.0022);Gain of catalytic residue at S622 (P = 0.0022);
MVP		0.37
MPC		0.85
ClinPred		0.44	T
GERP RS		5.4
Varity_R		0.19
gMVP		0.29

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: chr14-73577710;