19-5923252-C-T

Variant names:

• chr19-5923252-C-T
• NM_007322.3:c.1151G>A

Variant summary

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

The NM_007322.3(RANBP3):​c.1151G>A​(p.Cys384Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RANBP3 NM_007322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76
• Publications: 0 publications found

Genes affected

RANBP3 (HGNC:9850): (RAN binding protein 3) This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a heteromeric complex. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007322.3. 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
	RANBP3	NM_007322.3	MANE Select	c.1151G>A	p.Cys384Tyr	missense	Exon 13 of 17	NP_015561.1	Q9H6Z4-1
	RANBP3	NM_003624.3		c.1136G>A	p.Cys379Tyr	missense	Exon 13 of 17	NP_003615.2	Q9H6Z4-2
	RANBP3	NM_007320.3		c.947G>A	p.Cys316Tyr	missense	Exon 12 of 16	NP_015559.2	Q9H6Z4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP3	ENST00000340578.10	TSL:1 MANE Select	c.1151G>A	p.Cys384Tyr	missense	Exon 13 of 17	ENSP00000341483.5	Q9H6Z4-1
	RANBP3	ENST00000439268.6	TSL:1	c.1136G>A	p.Cys379Tyr	missense	Exon 13 of 17	ENSP00000404837.1	Q9H6Z4-2
	RANBP3	ENST00000034275.12	TSL:1	c.947G>A	p.Cys316Tyr	missense	Exon 12 of 16	ENSP00000034275.7	Q9H6Z4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Benign	0.48	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.29		Loss of catalytic residue at L385 (P = 0.018)
MVP		0.39
MPC		1.8
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.49
gMVP		0.54
Mutation Taster		=6/94	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: chr19-5923263;