chr20-35732031-C-T

Variant names:

• chr20-35732031-C-T
• rs750864321
• NM_184234.3:c.206G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001323423.2(RBM39):​c.-266G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000688 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: RBM39 NM_001323423.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28002188).
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323423.2. 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
	RBM39	NM_184234.3	MANE Select	c.206G>A	p.Arg69His	missense	Exon 4 of 17	NP_909122.1	Q14498-1
	RBM39	NM_001323423.2		c.-266G>A		5_prime_UTR_premature_start_codon_gain	Exon 6 of 19	NP_001310352.1
	RBM39	NM_001323424.2		c.206G>A	p.Arg69His	missense	Exon 4 of 17	NP_001310353.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM39	ENST00000253363.11	TSL:1 MANE Select	c.206G>A	p.Arg69His	missense	Exon 4 of 17	ENSP00000253363.6	Q14498-1
	RBM39	ENST00000361162.10	TSL:1	c.206G>A	p.Arg69His	missense	Exon 4 of 17	ENSP00000354437.6	Q14498-2
	RBM39	ENST00000528062.7	TSL:1	c.206G>A	p.Arg69His	missense	Exon 4 of 16	ENSP00000436747.2	Q14498-3

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152100 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251416 AF XY: 0.0000736

Gnomad AFR exome AF: 0.00

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: 0.0000704

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000698 AC: 102 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000818 AC: 91 AN: 1112008

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152100 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74308

African (AFR) AF: 0.0000483 AC: 2 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.21
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.22
Sift	Benign	0.088	T
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.28		Loss of helix (P = 0.079)
MVP		0.69
MPC		0.89
ClinPred		0.30	T
GERP RS		5.9
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.23
gMVP		0.58
Mutation Taster		=241/59	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: rs750864321; hg19: chr20-34319953;