5-72861812-T-C

Variant names:

• chr5-72861812-T-C
• rs768294052
• NM_002270.4:c.360T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_002270.4(TNPO1):​c.360T>C​(p.Ile120Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNPO1 NM_002270.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.82
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-72861812-T-C is Benign according to our data. Variant chr5-72861812-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3050401.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002270.4. 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
	TNPO1	NM_002270.4	MANE Select	c.360T>C	p.Ile120Ile	synonymous	Exon 5 of 25	NP_002261.3
	TNPO1	NM_001364292.3		c.336T>C	p.Ile112Ile	synonymous	Exon 5 of 25	NP_001351221.1	Q92973-2
	TNPO1	NM_001364293.3		c.336T>C	p.Ile112Ile	synonymous	Exon 5 of 25	NP_001351222.1	Q92973-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO1	ENST00000337273.10	TSL:1 MANE Select	c.360T>C	p.Ile120Ile	synonymous	Exon 5 of 25	ENSP00000336712.5	Q92973-1
	TNPO1	ENST00000506351.6	TSL:1	c.336T>C	p.Ile112Ile	synonymous	Exon 5 of 25	ENSP00000425118.2	Q92973-2
	TNPO1	ENST00000944758.1		c.426T>C	p.Ile142Ile	synonymous	Exon 5 of 25	ENSP00000614817.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459690 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726288

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110234

Other (OTH) AF: 0.0000332 AC: 2 AN: 60286

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TNPO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		1.8

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: rs768294052; hg19: chr5-72157639;