20-35717523-C-T

Position:

• chr20-35717523-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM39	NM_184234.3	c.826-718G>A		intron_variant		ENST00000253363.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM39	ENST00000253363.11	c.826-718G>A		intron_variant		1	NM_184234.3

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

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.112

Alfa AF: 0.108 Hom.: 133

Bravo AF: 0.105

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.48

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: rs6060578; hg19: chr20-34305445;