20-35732013-C-A

Variant names:

• chr20-35732013-C-A
• rs754134582
• NM_184234.3:c.224G>T

Variant summary

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

The NM_184234.3(RBM39):​c.224G>T​(p.Arg75Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RBM39 NM_184234.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64

Genes affected

RBM39 (HGNC:15923): (RNA binding motif protein 39) This gene encodes a member of the U2AF65 family of proteins. The encoded protein is found in the nucleus, where it co-localizes with core spliceosomal proteins. It has been shown to play a role in both steroid hormone receptor-mediated transcription and alternative splicing, and it is also a transcriptional coregulator of the viral oncoprotein v-Rel. Multiple transcript variants have been observed for this gene. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Aug 2011]

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
RBM39	NM_184234.3	c.224G>T	p.Arg75Ile	missense_variant	Exon 4 of 17	ENST00000253363.11	NP_909122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM39	ENST00000253363.11	c.224G>T	p.Arg75Ile	missense_variant	Exon 4 of 17	1	NM_184234.3	ENSP00000253363.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251472 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS 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: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D;.;.;.;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Uncertain	-0.081	T
MutationAssessor	Benign	1.8	L;L;L;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-4.8	D;D;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.025	D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;.;.
Polyphen		0.99	D;D;.;.;.
Vest4		0.53
MutPred		0.30		Loss of solvent accessibility (P = 0.0611);Loss of solvent accessibility (P = 0.0611);Loss of solvent accessibility (P = 0.0611);Loss of solvent accessibility (P = 0.0611);Loss of solvent accessibility (P = 0.0611);
MVP		0.65
MPC		1.6
ClinPred		0.99	D
GERP RS		5.9
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.8
Varity_R		0.55
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs754134582; hg19: chr20-34319935;