X-107088449-C-G

Variant names:

• chrX-107088449-C-G
• NM_001324242.2:c.986G>C

Variant summary

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

The NM_001324242.2(RBM41):​c.986G>C​(p.Gly329Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000729 in 1,096,907 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: RBM41 NM_001324242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM41	NM_001324242.2	c.986G>C	p.Gly329Ala	missense_variant	Exon 6 of 8	ENST00000685964.1	NP_001311171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM41	ENST00000685964.1	c.986G>C	p.Gly329Ala	missense_variant	Exon 6 of 8		NM_001324242.2	ENSP00000509650.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1096907 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362365

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000951

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.914G>C (p.G305A) alteration is located in exon 5 (coding exon 5) of the RBM41 gene. This alteration results from a G to C substitution at nucleotide position 914, causing the glycine (G) at amino acid position 305 to be replaced by an alanine (A). 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	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.53	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.82
MutPred		0.32		Loss of methylation at K309 (P = 0.103);Loss of methylation at K309 (P = 0.103);
MVP		0.76
MPC		0.71
ClinPred		0.99	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.95
gMVP		0.75

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: chrX-106331679;