19-5928072-T-C

Variant names:

• chr19-5928072-T-C
• NM_007322.3:c.709A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007322.3(RANBP3):​c.709A>G​(p.Lys237Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. 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: 4.09

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07706788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP3	NM_007322.3	c.709A>G	p.Lys237Glu	missense_variant	Exon 9 of 17	ENST00000340578.10	NP_015561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3	ENST00000340578.10	c.709A>G	p.Lys237Glu	missense_variant	Exon 9 of 17	1	NM_007322.3	ENSP00000341483.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.709A>G (p.K237E) alteration is located in exon 9 (coding exon 9) of the RANBP3 gene. This alteration results from a A to G substitution at nucleotide position 709, causing the lysine (K) at amino acid position 237 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.026	.;T;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.66	T;T;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.077	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	.;L;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.34	N;N;.;N;.
REVEL	Benign	0.032
Sift	Benign	0.42	T;T;.;T;.
Sift4G	Benign	0.25	T;T;T;T;.
Polyphen		0.0070	B;B;B;B;.
Vest4		0.093
MutPred		0.27		.;Loss of methylation at K237 (P = 0.0036);.;.;.;
MVP		0.43
MPC		0.68
ClinPred		0.41	T
GERP RS		4.2
Varity_R		0.17
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-5928083;