NM_002271.6:c.364+60_364+64delTTTTT

Variant names:

• chr13-97985663-CTTTTT-C
• rs11366582
• NM_002271.6:c.364+60_364+64delTTTTT

Variant summary

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

The NM_002271.6(IPO5):​c.364+60_364+64delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 785,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPO5	NM_002271.6	c.364+60_364+64delTTTTT		intron_variant	Intron 6 of 28	ENST00000651721.2	NP_002262.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPO5	ENST00000651721.2	c.364+51_364+55delTTTTT		intron_variant	Intron 6 of 28		NM_002271.6	ENSP00000499125.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000127 AC: 1 AN: 785964 Hom.: 0 AF XY: 0.00000245 AC XY: 1 AN XY: 408724

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16952

American (AMR) AF: 0.00 AC: 0 AN: 29186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18692

East Asian (EAS) AF: 0.00 AC: 0 AN: 33578

South Asian (SAS) AF: 0.00 AC: 0 AN: 58414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3338

European-Non Finnish (NFE) AF: 0.00000184 AC: 1 AN: 544896

Other (OTH) AF: 0.00 AC: 0 AN: 36340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48

Splicing

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

Other links and lift over

dbSNP: rs11366582; hg19: chr13-98637917;