chrX-107069280-C-G

Variant names:

• chrX-107069280-C-G
• NM_001324242.2:c.1122G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001324242.2(RBM41):​c.1122G>C​(p.Arg374Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RBM41 NM_001324242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457
• Publications: 0 publications found

Genes affected

RBM41 (HGNC:25617): (RNA binding motif protein 41) Predicted to enable U12 snRNA binding activity and pre-mRNA intronic binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324242.2. 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
	RBM41	NM_001324242.2	MANE Select	c.1122G>C	p.Arg374Ser	missense	Exon 7 of 8	NP_001311171.1	A0A8I5KYC8
	RBM41	NM_001324243.1		c.1227G>C	p.Arg409Ser	missense	Exon 7 of 8	NP_001311172.1
	RBM41	NM_001394116.1		c.1173G>C	p.Arg391Ser	missense	Exon 7 of 8	NP_001381045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM41	ENST00000685964.1	MANE Select	c.1122G>C	p.Arg374Ser	missense	Exon 7 of 8	ENSP00000509650.1	A0A8I5KYC8
	RBM41	ENST00000372479.8	TSL:1	c.1050G>C	p.Arg350Ser	missense	Exon 6 of 7	ENSP00000361557.3	Q96IZ5-1
	RBM41	ENST00000965480.1		c.1206G>C	p.Arg402Ser	missense	Exon 7 of 8	ENSP00000635539.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

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	0.82
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.46
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		0.88	P
Vest4		0.82
MutPred		0.79		Loss of methylation at R350 (P = 0.0087)
MVP		0.64
MPC		0.67
ClinPred		0.98	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.72
gMVP		0.77
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chrX-106312510;