rs4041421

Variant names:

• chr5-72831642-C-T
• rs4041421
• NM_002270.4:c.15+14890C>T

Variant summary

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

The NM_002270.4(TNPO1):​c.15+14890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,764 control chromosomes in the GnomAD database, including 18,270 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 0.47 (18270 hom., cov: 32)
• Consequence: TNPO1 NM_002270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 2 publications found

Genes affected

TNPO1 (HGNC:6401): (transportin 1) This gene encodes the beta subunit of the karyopherin receptor complex which interacts with nuclear localization signals to target nuclear proteins to the nucleus. The karyopherin receptor complex is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. Alternate splicing of this gene results in several transcript variants encoding different proteins. [provided by RefSeq, Jun 2018]

TNPO1 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO1	NM_002270.4	c.15+14890C>T		intron_variant	Intron 1 of 24	ENST00000337273.10	NP_002261.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO1	ENST00000337273.10	c.15+14890C>T		intron_variant	Intron 1 of 24	1	NM_002270.4	ENSP00000336712.5

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71868 AN: 151648 Hom.: 18255 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.507

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.474 AC: 71907 AN: 151764 Hom.: 18270 Cov.: 32 AF XY: 0.478 AC XY: 35409 AN XY: 74130

African (AFR) AF: 0.273 AC: 11317 AN: 41482

American (AMR) AF: 0.607 AC: 9252 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3468

East Asian (EAS) AF: 0.404 AC: 2088 AN: 5172

South Asian (SAS) AF: 0.525 AC: 2529 AN: 4816

European-Finnish (FIN) AF: 0.584 AC: 6137 AN: 10504

Middle Eastern (MID) AF: 0.586 AC: 164 AN: 280

European-Non Finnish (NFE) AF: 0.544 AC: 36846 AN: 67784

Other (OTH) AF: 0.510 AC: 1075 AN: 2106

Alfa AF: 0.481 Hom.: 2590

Bravo AF: 0.466

Asia WGS AF: 0.473 AC: 1619 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.65
PhyloP100		-1.7
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: rs4041421; hg19: chr5-72127469;