rs1263430014

Variant names:

• chrX-107088659-A-G
• rs1263430014
• NM_001324242.2:c.776T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001324242.2(RBM41):​c.776T>C​(p.Leu259Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000091 in 1,209,334 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: RBM41 NM_001324242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 1 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_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07230958).

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.776T>C	p.Leu259Ser	missense	Exon 6 of 8	NP_001311171.1	A0A8I5KYC8
	RBM41	NM_001324243.1		c.881T>C	p.Leu294Ser	missense	Exon 6 of 8	NP_001311172.1
	RBM41	NM_001394116.1		c.827T>C	p.Leu276Ser	missense	Exon 6 of 8	NP_001381045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM41	ENST00000685964.1	MANE Select	c.776T>C	p.Leu259Ser	missense	Exon 6 of 8	ENSP00000509650.1	A0A8I5KYC8
	RBM41	ENST00000372479.8	TSL:1	c.704T>C	p.Leu235Ser	missense	Exon 5 of 7	ENSP00000361557.3	Q96IZ5-1
	RBM41	ENST00000965480.1		c.860T>C	p.Leu287Ser	missense	Exon 6 of 8	ENSP00000635539.1

Frequencies

GnomAD3 genomes AF: 0.0000360 AC: 4 AN: 111263 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000382

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183334 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000637 AC: 7 AN: 1098071 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363425

African (AFR) AF: 0.0000379 AC: 1 AN: 26400

American (AMR) AF: 0.000142 AC: 5 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841986

Other (OTH) AF: 0.0000217 AC: 1 AN: 46090

GnomAD4 genome AF: 0.0000360 AC: 4 AN: 111263 Hom.: 0 Cov.: 22 AF XY: 0.0000299 AC XY: 1 AN XY: 33463

African (AFR) AF: 0.00 AC: 0 AN: 30546

American (AMR) AF: 0.000382 AC: 4 AN: 10467

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3534

South Asian (SAS) AF: 0.00 AC: 0 AN: 2611

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5999

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53067

Other (OTH) AF: 0.00 AC: 0 AN: 1479

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

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	Benign	0.081
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.10
Sift	Benign	0.76	T
Sift4G	Benign	0.56	T
Polyphen		0.013	B
Vest4		0.19
MutPred		0.36		Loss of stability (P = 0.0058)
MVP		0.61
MPC		0.23
ClinPred		0.098	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.29
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1263430014; hg19: chrX-106331889;