20-35717523-C-T

Variant names:

• chr20-35717523-C-T
• rs6060578
• NM_184234.3:c.826-718G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_184234.3(RBM39):​c.826-718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,996 control chromosomes in the GnomAD database, including 866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (866 hom., cov: 31)
• Consequence: RBM39 NM_184234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 25 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_184234.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM39	NM_184234.3	MANE Select	c.826-718G>A		intron	N/A	NP_909122.1
	RBM39	NM_001323424.2		c.823-718G>A		intron	N/A	NP_001310353.1
	RBM39	NM_004902.4		c.826-718G>A		intron	N/A	NP_004893.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM39	ENST00000253363.11	TSL:1 MANE Select	c.826-718G>A		intron	N/A	ENSP00000253363.6
	RBM39	ENST00000361162.10	TSL:1	c.826-718G>A		intron	N/A	ENSP00000354437.6
	RBM39	ENST00000528062.7	TSL:1	c.760-718G>A		intron	N/A	ENSP00000436747.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15916 AN: 151878 Hom.: 865 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15922 AN: 151996 Hom.: 866 Cov.: 31 AF XY: 0.103 AC XY: 7684 AN XY: 74292

African (AFR) AF: 0.104 AC: 4317 AN: 41482

American (AMR) AF: 0.111 AC: 1690 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3464

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5172

South Asian (SAS) AF: 0.143 AC: 691 AN: 4822

European-Finnish (FIN) AF: 0.0827 AC: 872 AN: 10540

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7151 AN: 67950

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.108 Hom.: 138

Bravo AF: 0.105

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.48
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs6060578; hg19: chr20-34305445;