19-12701448-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001382241.1(TNPO2):c.2592C>T(p.Leu864=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,613,834 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (43 hom.)
• Consequence: TNPO2 NM_001382241.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.52

Genes affected

TNPO2 (HGNC:19998): (transportin 2) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Predicted to act upstream of or within negative regulation of muscle cell differentiation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-12701448-G-A is Benign according to our data. Variant chr19-12701448-G-A is described in ClinVar as [Benign]. Clinvar id is 777899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.52 with no splicing effect.
• BS2: High AC in GnomAd at 918 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO2	NM_001382241.1	c.2592C>T	p.Leu864=	synonymous_variant	25/26	ENST00000425528.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO2	ENST00000425528.6	c.2592C>T	p.Leu864=	synonymous_variant	25/26	5	NM_001382241.1

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 918 AN: 152100 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00663 AC: 1652 AN: 249166 Hom.: 16 AF XY: 0.00677 AC XY: 915 AN XY: 135200

Gnomad AFR exome AF: 0.000969

Gnomad AMR exome AF: 0.00516

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.00626

Gnomad OTH exome AF: 0.00926

GnomAD4 exome AF: 0.00573 AC: 8377 AN: 1461616 Hom.: 43 Cov.: 31 AF XY: 0.00565 AC XY: 4106 AN XY: 727110

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00564

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.0243

Gnomad4 NFE exome AF: 0.00544

Gnomad4 OTH exome AF: 0.00593

GnomAD4 genome AF: 0.00604 AC: 919 AN: 152218 Hom.: 11 Cov.: 32 AF XY: 0.00688 AC XY: 512 AN XY: 74414

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.00615

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00576 Hom.: 1

Bravo AF: 0.00446

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00522

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	TNPO2: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	5.2
Dann	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs185580176; hg19: chr19-12812262;