chr19-5925706-A-G

Variant names:

• chr19-5925706-A-G
• rs775002515
• NM_007322.3:c.845T>C

Variant summary

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

The NM_007322.3(RANBP3):​c.845T>C​(p.Met282Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RANBP3 NM_007322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.80
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14800826).

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.845T>C	p.Met282Thr	missense	Exon 10 of 17	NP_015561.1	Q9H6Z4-1
	RANBP3	NM_003624.3		c.830T>C	p.Met277Thr	missense	Exon 10 of 17	NP_003615.2	Q9H6Z4-2
	RANBP3	NM_007320.3		c.641T>C	p.Met214Thr	missense	Exon 9 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.845T>C	p.Met282Thr	missense	Exon 10 of 17	ENSP00000341483.5	Q9H6Z4-1
	RANBP3	ENST00000439268.6	TSL:1	c.830T>C	p.Met277Thr	missense	Exon 10 of 17	ENSP00000404837.1	Q9H6Z4-2
	RANBP3	ENST00000034275.12	TSL:1	c.641T>C	p.Met214Thr	missense	Exon 9 of 16	ENSP00000034275.7	Q9H6Z4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.065
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.37
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.055
Sift	Benign	0.48	T
Sift4G	Benign	0.59	T
Polyphen		0.012	B
Vest4		0.35
MutPred		0.23		Gain of phosphorylation at M282 (P = 0.0524)
MVP		0.38
MPC		0.56
ClinPred		0.076	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.17
Mutation Taster		=94/6	polymorphism

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: rs775002515; hg19: chr19-5925717;