14-73103468-A-G

Position:

• chr14-73103468-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000261973.12(RBM25):​c.1144A>G​(p.Ser382Gly) 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)
• Consequence: RBM25 ENST00000261973.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81

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]

RBM25 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30919862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM25	NM_021239.3	c.1144A>G	p.Ser382Gly	missense_variant	10/19	ENST00000261973.12	NP_067062.1
RBM25	XM_011537044.4	c.1144A>G	p.Ser382Gly	missense_variant	11/20		XP_011535346.1
RBM25	XM_047431641.1	c.1144A>G	p.Ser382Gly	missense_variant	10/16		XP_047287597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM25	ENST00000261973.12	c.1144A>G	p.Ser382Gly	missense_variant	10/19	1	NM_021239.3	ENSP00000261973.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 15, 2024

The c.1144A>G (p.S382G) alteration is located in exon 10 (coding exon 9) of the RBM25 gene. This alteration results from a A to G substitution at nucleotide position 1144, causing the serine (S) at amino acid position 382 to be replaced by a glycine (G). 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	0.31
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.27
Sift	Benign	0.11	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.92	P;P
Vest4		0.33
MutPred		0.33		Loss of phosphorylation at S382 (P = 0);Loss of phosphorylation at S382 (P = 0);
MVP		0.44
MPC		0.98
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.22
gMVP		0.028

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: chr14-73570176;