NM_022897.5:c.547A>T

Variant names:

• chr5-170909718-A-T
• rs148659070
• NM_022897.5:c.547A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_022897.5(RANBP17):​c.547A>T​(p.Thr183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,597,752 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00047 (7 hom.)
• Consequence: RANBP17 NM_022897.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.40
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047468245).
• BP6: Variant 5-170909718-A-T is Benign according to our data. Variant chr5-170909718-A-T is described in ClinVar as Benign. ClinVar VariationId is 3049366.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00478 (722/150990) while in subpopulation AFR AF = 0.0169 (700/41316). AF 95% confidence interval is 0.0159. There are 4 homozygotes in GnomAd4. There are 327 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.547A>T	p.Thr183Ser	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.547A>T	p.Thr183Ser	missense	Exon 6 of 28	ENSP00000427975.1	Q9H2T7-1
	RANBP17	ENST00000519130.5	TSL:1	n.558A>T		non_coding_transcript_exon	Exon 6 of 6
	RANBP17	ENST00000961946.1		c.547A>T	p.Thr183Ser	missense	Exon 6 of 29	ENSP00000632005.1

Frequencies

GnomAD3 genomes AF: 0.00479 AC: 722 AN: 150876 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000866

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000888

Gnomad OTH AF: 0.000967

GnomAD2 exomes AF: 0.00117 AC: 291 AN: 247914 AF XY: 0.000820

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000504

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000473 AC: 685 AN: 1446762 Hom.: 7 Cov.: 27 AF XY: 0.000366 AC XY: 264 AN XY: 720496

African (AFR) AF: 0.0181 AC: 594 AN: 32882

American (AMR) AF: 0.000520 AC: 23 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5718

European-Non Finnish (NFE) AF: 0.0000127 AC: 14 AN: 1100346

Other (OTH) AF: 0.000870 AC: 52 AN: 59804

GnomAD4 genome AF: 0.00478 AC: 722 AN: 150990 Hom.: 4 Cov.: 31 AF XY: 0.00443 AC XY: 327 AN XY: 73734

African (AFR) AF: 0.0169 AC: 700 AN: 41316

American (AMR) AF: 0.000865 AC: 13 AN: 15028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000888 AC: 6 AN: 67554

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000515 Hom.: 0

Bravo AF: 0.00543

ESP6500AA AF: 0.0182 AC: 80

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00144 AC: 175

Asia WGS AF: 0.000867 AC: 3 AN: 3476

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

ClinVar submissions

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	Benign	0.076
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.2
DANN	Benign	0.76
DEOGEN2	Benign	0.00096	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.030
Sift	Benign	1.0	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.19		Gain of disorder (P = 0.0467)
MVP		0.57
MPC		0.025
ClinPred		0.0092	T
GERP RS		2.7
Varity_R		0.051
gMVP		0.18
Mutation Taster		=100/0	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: rs148659070; hg19: chr5-170336722;