chr5-170909751-T-G

Variant names:

• chr5-170909751-T-G
• NM_022897.5:c.580T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022897.5(RANBP17):​c.580T>G​(p.Ser194Ala) 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. 14/22 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: 3.21
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2626422).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022897.5. 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
	RANBP17	NM_022897.5	MANE Select	c.580T>G	p.Ser194Ala	missense	Exon 6 of 28	NP_075048.1	Q546R4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANBP17	ENST00000523189.6	TSL:1 MANE Select	c.580T>G	p.Ser194Ala	missense	Exon 6 of 28	ENSP00000427975.1	Q9H2T7-1
	RANBP17	ENST00000519130.5	TSL:1	n.591T>G		non_coding_transcript_exon	Exon 6 of 6
	RANBP17	ENST00000961946.1		c.580T>G	p.Ser194Ala	missense	Exon 6 of 29	ENSP00000632005.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 31

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	0.082
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.17
Sift	Uncertain	0.013	D
Sift4G	Benign	0.083	T
Polyphen		0.35	B
Vest4		0.46
MutPred		0.37		Gain of ubiquitination at K197 (P = 0.086)
MVP		0.75
MPC		0.081
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.22
gMVP		0.16
Mutation Taster		=93/7	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

hg19: chr5-170336755;