chr13-98006356-A-ATTTTT

Variant names:

• chr13-98006356-A-ATTTTT
• rs568589408
• NM_002271.6:c.1716+40_1716+44dupTTTTT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002271.6(IPO5):​c.1716+40_1716+44dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (42 hom., cov: 0)
  • Exomes 𝑓: 0.00052 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: IPO5 NM_002271.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 13-98006356-A-ATTTTT is Benign according to our data. Variant chr13-98006356-A-ATTTTT is described in ClinVar as Likely_benign. ClinVar VariationId is 2643882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 42 gene

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.1716+40_1716+44dupTTTTT		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.1716+8_1716+9insTTTTT		intron	N/A	ENSP00000499125.1	O00410-1
	IPO5	ENST00000261574.10	TSL:1	c.1770+8_1770+9insTTTTT		intron	N/A	ENSP00000261574.5	O00410-3
	IPO5	ENST00000490680.5	TSL:1	c.1716+8_1716+9insTTTTT		intron	N/A	ENSP00000418393.1	O00410-1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 132 AN: 62844 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.00950

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000529

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000539

Gnomad OTH AF: 0.00122

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000516 AC: 255 AN: 493922 Hom.: 3 Cov.: 0 AF XY: 0.000513 AC XY: 134 AN XY: 261160

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

African (AFR) AF: 0.000701 AC: 4 AN: 5710

American (AMR) AF: 0.000170 AC: 3 AN: 17606

Ashkenazi Jewish (ASJ) AF: 0.000456 AC: 5 AN: 10954

East Asian (EAS) AF: 0.000159 AC: 3 AN: 18816

South Asian (SAS) AF: 0.00131 AC: 63 AN: 47962

European-Finnish (FIN) AF: 0.000426 AC: 12 AN: 28164

Middle Eastern (MID) AF: 0.000350 AC: 1 AN: 2856

European-Non Finnish (NFE) AF: 0.000429 AC: 146 AN: 340542

Other (OTH) AF: 0.000845 AC: 18 AN: 21312

⚠️ 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 AF: 0.00210 AC: 132 AN: 62854 Hom.: 42 Cov.: 0 AF XY: 0.00227 AC XY: 64 AN XY: 28154

African (AFR) AF: 0.00948 AC: 110 AN: 11602

American (AMR) AF: 0.00 AC: 0 AN: 4472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2148

East Asian (EAS) AF: 0.00 AC: 0 AN: 2446

South Asian (SAS) AF: 0.000530 AC: 1 AN: 1886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.000539 AC: 20 AN: 37132

Other (OTH) AF: 0.00120 AC: 1 AN: 830

Alfa AF: 0.00 Hom.: 53

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs568589408; hg19: chr13-98658610;