chr20-35724691-T-C

Variant names:

• chr20-35724691-T-C
• NM_184234.3:c.566A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_184234.3(RBM39):​c.566A>G​(p.Asn189Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM39 NM_184234.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.01
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35365856).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM39	NM_184234.3	MANE Select	c.566A>G	p.Asn189Ser	missense	Exon 8 of 17	NP_909122.1	Q14498-1
	RBM39	NM_001323424.2		c.563A>G	p.Asn188Ser	missense	Exon 8 of 17	NP_001310353.1
	RBM39	NM_004902.4		c.566A>G	p.Asn189Ser	missense	Exon 8 of 17	NP_004893.1	Q14498-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM39	ENST00000253363.11	TSL:1 MANE Select	c.566A>G	p.Asn189Ser	missense	Exon 8 of 17	ENSP00000253363.6	Q14498-1
	RBM39	ENST00000361162.10	TSL:1	c.566A>G	p.Asn189Ser	missense	Exon 8 of 17	ENSP00000354437.6	Q14498-2
	RBM39	ENST00000528062.7	TSL:1	c.500A>G	p.Asn167Ser	missense	Exon 7 of 16	ENSP00000436747.2	Q14498-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.48
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		8.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Benign	0.061	T
Sift4G	Benign	0.14	T
Polyphen		0.77	P
Vest4		0.49
MutPred		0.39		Gain of phosphorylation at N189 (P = 0.0054)
MVP		0.71
MPC		1.9
ClinPred		0.71	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.73
Mutation Taster		=25/75	disease causing

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

hg19: chr20-34312613;