rs200106292

Variant names:

• chrX-107067597-C-A
• rs200106292
• NM_001324242.2:c.1244G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-107067597-C-A
• chrX-107067597-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001324242.2(RBM41):​c.1244G>T​(p.Arg415Leu) 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 1,208,793 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R415Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: RBM41 NM_001324242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.16
• Publications: 4 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045901597).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

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.1244G>T	p.Arg415Leu	missense	Exon 8 of 8	NP_001311171.1	A0A8I5KYC8
	RBM41	NM_001324243.1		c.1349G>T	p.Arg450Leu	missense	Exon 8 of 8	NP_001311172.1
	RBM41	NM_001394116.1		c.1295G>T	p.Arg432Leu	missense	Exon 8 of 8	NP_001381045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM41	ENST00000685964.1	MANE Select	c.1244G>T	p.Arg415Leu	missense	Exon 8 of 8	ENSP00000509650.1	A0A8I5KYC8
	RBM41	ENST00000372479.8	TSL:1	c.1172G>T	p.Arg391Leu	missense	Exon 7 of 7	ENSP00000361557.3	Q96IZ5-1
	RBM41	ENST00000965480.1		c.1328G>T	p.Arg443Leu	missense	Exon 8 of 8	ENSP00000635539.1

Frequencies

GnomAD3 genomes AF: 0.0000448 AC: 5 AN: 111503 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000476

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: 0.0000164 AC: 3 AN: 182916 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000110

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: 0.00000547 AC: 6 AN: 1097237 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 362803

African (AFR) AF: 0.00 AC: 0 AN: 26371

American (AMR) AF: 0.0000853 AC: 3 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19352

East Asian (EAS) AF: 0.00 AC: 0 AN: 30166

South Asian (SAS) AF: 0.00 AC: 0 AN: 53963

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841530

Other (OTH) AF: 0.0000652 AC: 3 AN: 46044

GnomAD4 genome AF: 0.0000448 AC: 5 AN: 111556 Hom.: 0 Cov.: 23 AF XY: 0.0000887 AC XY: 3 AN XY: 33814

African (AFR) AF: 0.00 AC: 0 AN: 30802

American (AMR) AF: 0.000476 AC: 5 AN: 10509

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52936

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

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	0.074
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.85
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-3.2
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.060
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.091
MutPred		0.50		Loss of MoRF binding (P = 0.0239)
MVP		0.49
MPC		0.20
ClinPred		0.063	T
GERP RS		-11
Varity_R		0.045
gMVP		0.41
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs200106292; hg19: chrX-106310827;