6-13639740-T-A

Variant names:

• chr6-13639740-T-A
• NM_005493.3:c.1348A>T

Variant summary

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

The NM_005493.3(RANBP9):​c.1348A>T​(p.Ile450Leu) 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: 32)
• Consequence: RANBP9 NM_005493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15

Genes affected

RANBP9 (HGNC:13727): (RAN binding protein 9) This gene encodes a protein that binds RAN, a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The protein encoded by this gene has also been shown to interact with several other proteins, including met proto-oncogene, homeodomain interacting protein kinase 2, androgen receptor, and cyclin-dependent kinase 11. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP9	NM_005493.3	c.1348A>T	p.Ile450Leu	missense_variant	Exon 9 of 14	ENST00000011619.6	NP_005484.2
RANBP9	XM_011514205.3	c.1348A>T	p.Ile450Leu	missense_variant	Exon 9 of 12		XP_011512507.1
RANBP9	XM_017010149.2	c.682A>T	p.Ile228Leu	missense_variant	Exon 9 of 14		XP_016865638.1
RANBP9	XM_047418032.1	c.661A>T	p.Ile221Leu	missense_variant	Exon 9 of 14		XP_047273988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP9	ENST00000011619.6	c.1348A>T	p.Ile450Leu	missense_variant	Exon 9 of 14	1	NM_005493.3	ENSP00000011619.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1348A>T (p.I450L) alteration is located in exon 9 (coding exon 9) of the RANBP9 gene. This alteration results from a A to T substitution at nucleotide position 1348, causing the isoleucine (I) at amino acid position 450 to be replaced by a leucine (L). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Benign	1.7	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.9	N
REVEL	Pathogenic	0.65
Sift	Benign	0.12	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.82	P
Vest4		0.73
MutPred		0.53		Gain of disorder (P = 0.0499);
MVP		0.76
MPC		1.9
ClinPred		0.93	D
GERP RS		5.3
Varity_R		0.33
gMVP		0.78

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: chr6-13639972;