5-170892431-C-A

Position:

• chr5-170892431-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

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]

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=0.1640186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RANBP17	NM_022897.5	c.301C>A	p.Pro101Thr	missense_variant	4/28	ENST00000523189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RANBP17	ENST00000523189.6	c.301C>A	p.Pro101Thr	missense_variant	4/28	1	NM_022897.5	P1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The 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;