5-170862046-T-C

Variant names:

• chr5-170862046-T-C
• rs139675546
• NM_022897.5:c.13T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_022897.5(RANBP17):​c.13T>C​(p.Phe5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 1,463,894 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 34)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: RANBP17 NM_022897.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.40
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004602313).
• BP6: Variant 5-170862046-T-C is Benign according to our data. Variant chr5-170862046-T-C is described in ClinVar as Benign. ClinVar VariationId is 3056422.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.13T>C	p.Phe5Leu	missense	Exon 1 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.13T>C	p.Phe5Leu	missense	Exon 1 of 28	ENSP00000427975.1	Q9H2T7-1
	RANBP17	ENST00000519130.5	TSL:1	n.24T>C		non_coding_transcript_exon	Exon 1 of 6
	RANBP17	ENST00000961946.1		c.13T>C	p.Phe5Leu	missense	Exon 1 of 29	ENSP00000632005.1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 619 AN: 152070 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

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: 0.000955

GnomAD2 exomes AF: 0.000201 AC: 14 AN: 69792 AF XY: 0.000149

Gnomad AFR exome AF: 0.00569

Gnomad AMR exome AF: 0.000679

Gnomad ASJ exome AF: 0.00

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: 0.000393 AC: 515 AN: 1311716 Hom.: 2 Cov.: 31 AF XY: 0.000331 AC XY: 214 AN XY: 646316

African (AFR) AF: 0.0148 AC: 391 AN: 26494

American (AMR) AF: 0.000695 AC: 17 AN: 24444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23078

East Asian (EAS) AF: 0.00 AC: 0 AN: 27868

South Asian (SAS) AF: 0.0000697 AC: 5 AN: 71710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3972

European-Non Finnish (NFE) AF: 0.0000458 AC: 48 AN: 1046996

Other (OTH) AF: 0.000991 AC: 54 AN: 54486

GnomAD4 genome AF: 0.00407 AC: 620 AN: 152178 Hom.: 5 Cov.: 34 AF XY: 0.00403 AC XY: 300 AN XY: 74406

African (AFR) AF: 0.0144 AC: 598 AN: 41548

American (AMR) AF: 0.00124 AC: 19 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67978

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00433

ExAC AF: 0.000261 AC: 4

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RANBP17-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.00045	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.050
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.27		Loss of catalytic residue at F5 (P = 0.0722)
MVP		0.15
MPC		0.028
ClinPred		0.025	T
GERP RS		2.4
PromoterAI		-0.27	Neutral
Varity_R		0.078
gMVP		0.16
Mutation Taster		=98/2	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: rs139675546; hg19: chr5-170289050; COSMIC: COSV66644287; COSMIC: COSV66644287;