NM_005493.3:c.1885G>A

Variant names:

• chr6-13632432-C-T
• rs982981511
• NM_005493.3:c.1885G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_005493.3(RANBP9):​c.1885G>A​(p.Ala629Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RANBP9 NM_005493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

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]

NOL7 (HGNC:21040): (nucleolar protein 7) The protein encoded by this gene localizes to the nucleolus, where it maintains nucleolar structure and cell growth rates. The encoded protein also functions as a tumor suppressor and regulator of angiogenesis. The RB tumor suppressor gene recruits transcription factors to this gene and positively regulates its expression. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26837695).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005493.3. 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
	RANBP9	NM_005493.3	MANE Select	c.1885G>A	p.Ala629Thr	missense	Exon 12 of 14	NP_005484.2
	NOL7	NM_001317724.2		c.*69C>T		3_prime_UTR	Exon 9 of 9	NP_001304653.1	Q9UMY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP9	ENST00000011619.6	TSL:1 MANE Select	c.1885G>A	p.Ala629Thr	missense	Exon 12 of 14	ENSP00000011619.3	Q96S59-1
	RANBP9	ENST00000940147.1		c.1882G>A	p.Ala628Thr	missense	Exon 12 of 14	ENSP00000610206.1
	RANBP9	ENST00000962251.1		c.1861G>A	p.Ala621Thr	missense	Exon 12 of 14	ENSP00000632310.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251312 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461786 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111934

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 29

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.41	N
REVEL	Uncertain	0.31
Sift	Benign	0.12	T
Sift4G	Benign	0.58	T
Polyphen		0.25	B
Vest4		0.49
MutPred		0.53		Gain of phosphorylation at A629 (P = 0.0665)
MVP		0.56
MPC		0.038
ClinPred		0.47	T
GERP RS		5.2
Varity_R		0.25
gMVP		0.20
Mutation Taster		=59/41	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: rs982981511; hg19: chr6-13632664;