5-170892431-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022897.5(RANBP17):​c.301C>A​(p.Pro101Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

RANBP17
NM_022897.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.46
Variant links:
Genes affected
RANBP17 (HGNC:14428): (RAN binding protein 17) The transport of protein and large RNAs through the nuclear pore complexes (NPC) is an energy-dependent and regulated process. The import of proteins with a nuclear localization signal (NLS) is accomplished by recognition of one or more clusters of basic amino acids by the importin-alpha/beta complex; see MIM 600685 and MIM 602738. The small GTPase RAN (MIM 601179) plays a key role in NLS-dependent protein import. RAN-binding protein-17 is a member of the importin-beta superfamily of nuclear transport receptors.[supplied by OMIM, Jul 2002]

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ACMG classification

Classification made for transcript

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=0.1640186).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RANBP17NM_022897.5 linkuse as main transcriptc.301C>A p.Pro101Thr missense_variant 4/28 ENST00000523189.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RANBP17ENST00000523189.6 linkuse as main transcriptc.301C>A p.Pro101Thr missense_variant 4/281 NM_022897.5 P1Q9H2T7-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2021The c.301C>A (p.P101T) alteration is located in exon 4 (coding exon 4) of the RANBP17 gene. This alteration results from a C to A substitution at nucleotide position 301, causing the proline (P) at amino acid position 101 to be replaced by a threonine (T). 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
0.11
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Benign
0.82
DEOGEN2
Benign
0.0046
T;.
Eigen
Benign
-0.17
Eigen_PC
Benign
0.018
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
0.98
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.79
N;N
REVEL
Benign
0.042
Sift
Benign
0.52
T;T
Sift4G
Benign
0.94
T;T
Polyphen
0.0050
B;.
Vest4
0.37
MutPred
0.39
Loss of stability (P = 0.092);.;
MVP
0.74
MPC
0.12
ClinPred
0.65
D
GERP RS
5.0
Varity_R
0.083
gMVP
0.23

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: chr5-170319435; API