rs188045006

Variant names:

• chr19-5918573-C-G
• rs188045006
• NM_007322.3:c.1396G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-5918573-C-G
• chr19-5918573-C-T

Variant summary

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

The NM_007322.3(RANBP3):​c.1396G>C​(p.Asp466His) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,016 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D466N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: RANBP3 NM_007322.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74

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 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
RANBP3	NM_007322.3	c.1396G>C	p.Asp466His	missense_variant	Exon 15 of 17	ENST00000340578.10	NP_015561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3	ENST00000340578.10	c.1396G>C	p.Asp466His	missense_variant	Exon 15 of 17	1	NM_007322.3	ENSP00000341483.5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152016 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74244

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.15	.;N;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	N;N;.;N;.
REVEL	Uncertain	0.32
Sift	Benign	0.034	D;D;.;D;.
Sift4G	Uncertain	0.035	D;D;D;D;D
Polyphen		1.0	D;D;D;D;.
Vest4		0.79
MutPred		0.42		.;Gain of sheet (P = 0.0149);.;.;.;
MVP		0.49
MPC		1.5
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.63
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs188045006; hg19: chr19-5918584;