chr20-35729327-T-C

Variant names:

• chr20-35729327-T-C
• rs2039112743
• NM_184234.3:c.401A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_184234.3(RBM39):​c.401A>G​(p.Asp134Gly) variant causes a missense change. 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: 6.39
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22463262).

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.401A>G	p.Asp134Gly	missense	Exon 6 of 17	NP_909122.1	Q14498-1
	RBM39	NM_001323424.2		c.398A>G	p.Asp133Gly	missense	Exon 6 of 17	NP_001310353.1
	RBM39	NM_004902.4		c.401A>G	p.Asp134Gly	missense	Exon 6 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.401A>G	p.Asp134Gly	missense	Exon 6 of 17	ENSP00000253363.6	Q14498-1
	RBM39	ENST00000361162.10	TSL:1	c.401A>G	p.Asp134Gly	missense	Exon 6 of 17	ENSP00000354437.6	Q14498-2
	RBM39	ENST00000528062.7	TSL:1	c.335A>G	p.Asp112Gly	missense	Exon 5 of 16	ENSP00000436747.2	Q14498-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.43
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.17
Sift	Benign	0.27	T
Sift4G	Benign	0.29	T
Polyphen		0.034	B
Vest4		0.33
MutPred		0.30		Gain of MoRF binding (P = 0.0364)
MVP		0.73
MPC		1.0
ClinPred		0.66	D
GERP RS		5.5
PromoterAI		0.0050	Neutral
Varity_R		0.29
gMVP		0.66
Mutation Taster		=246/54	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2039112743; hg19: chr20-34317249;