chr13-97985677-T-A

Variant names:

• chr13-97985677-T-A
• rs60936969
• NM_002271.6:c.364+64T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002271.6(IPO5):​c.364+64T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,063,980 control chromosomes in the GnomAD database, including 107,490 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (10375 hom., cov: 30)
  • Exomes 𝑓: 0.45 (97115 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 1 publications found

Genes affected

IPO5 (HGNC:6402): (importin 5) Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex. The protein encoded by this gene is a member of the importin beta family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002271.6. 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
	IPO5	NM_002271.6	MANE Select	c.364+64T>A		intron	N/A	NP_002262.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPO5	ENST00000651721.2	MANE Select	c.364+64T>A		intron	N/A	ENSP00000499125.1	O00410-1
	IPO5	ENST00000261574.10	TSL:1	c.418+64T>A		intron	N/A	ENSP00000261574.5	O00410-3
	IPO5	ENST00000490680.5	TSL:1	c.364+64T>A		intron	N/A	ENSP00000418393.1	O00410-1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 49306 AN: 147994 Hom.: 10376 Cov.: 30

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.448 AC: 410181 AN: 915876 Hom.: 97115 AF XY: 0.448 AC XY: 212222 AN XY: 474206

African (AFR) AF: 0.0852 AC: 1566 AN: 18386

American (AMR) AF: 0.280 AC: 9517 AN: 34046

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 8218 AN: 21072

East Asian (EAS) AF: 0.0154 AC: 545 AN: 35310

South Asian (SAS) AF: 0.370 AC: 24529 AN: 66328

European-Finnish (FIN) AF: 0.478 AC: 24037 AN: 50290

Middle Eastern (MID) AF: 0.361 AC: 1320 AN: 3654

European-Non Finnish (NFE) AF: 0.501 AC: 323532 AN: 645642

Other (OTH) AF: 0.411 AC: 16917 AN: 41148

GnomAD4 genome AF: 0.333 AC: 49295 AN: 148104 Hom.: 10375 Cov.: 30 AF XY: 0.330 AC XY: 23868 AN XY: 72262

African (AFR) AF: 0.0901 AC: 3478 AN: 38604

American (AMR) AF: 0.312 AC: 4701 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1282 AN: 3450

East Asian (EAS) AF: 0.0228 AC: 116 AN: 5082

South Asian (SAS) AF: 0.336 AC: 1593 AN: 4744

European-Finnish (FIN) AF: 0.477 AC: 4861 AN: 10200

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.475 AC: 32114 AN: 67676

Other (OTH) AF: 0.313 AC: 649 AN: 2076

Alfa AF: 0.396 Hom.: 1659

Bravo AF: 0.302

Asia WGS AF: 0.167 AC: 579 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.44
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60936969; hg19: chr13-98637931;