19-12700565-T-C

Variant names:

• chr19-12700565-T-C
• rs722571
• NM_001382241.1:c.*699A>G

Variant summary

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

The NM_001382241.1(TNPO2):​c.*699A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,392 control chromosomes in the GnomAD database, including 17,623 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 (17609 hom., cov: 28)
  • Exomes 𝑓: 0.45 (14 hom.)
• Consequence: TNPO2 NM_001382241.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 17 publications found

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]

TNPO2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382241.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO2	NM_001382241.1	MANE Select	c.*699A>G		3_prime_UTR	Exon 26 of 26	NP_001369170.1
	TNPO2	NR_167974.1		n.3504A>G		non_coding_transcript_exon	Exon 25 of 25
	TNPO2	NR_167975.1		n.3629A>G		non_coding_transcript_exon	Exon 26 of 26

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO2	ENST00000425528.6	TSL:5 MANE Select	c.*699A>G		3_prime_UTR	Exon 26 of 26	ENSP00000407182.1
	TNPO2	ENST00000356861.9	TSL:1	c.*699A>G		3_prime_UTR	Exon 25 of 25	ENSP00000349321.4
	TNPO2	ENST00000450764.6	TSL:1	c.*699A>G		3_prime_UTR	Exon 24 of 24	ENSP00000397379.2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70571 AN: 151128 Hom.: 17589 Cov.: 28

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.452 AC: 66 AN: 146 Hom.: 14 Cov.: 0 AF XY: 0.443 AC XY: 47 AN XY: 106

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.466 AC: 55 AN: 118

Other (OTH) AF: 0.417 AC: 5 AN: 12

GnomAD4 genome AF: 0.467 AC: 70614 AN: 151246 Hom.: 17609 Cov.: 28 AF XY: 0.454 AC XY: 33529 AN XY: 73856

African (AFR) AF: 0.624 AC: 25655 AN: 41132

American (AMR) AF: 0.402 AC: 6097 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1896 AN: 3470

East Asian (EAS) AF: 0.166 AC: 853 AN: 5134

South Asian (SAS) AF: 0.287 AC: 1373 AN: 4792

European-Finnish (FIN) AF: 0.275 AC: 2873 AN: 10442

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30374 AN: 67832

Other (OTH) AF: 0.484 AC: 1009 AN: 2084

Alfa AF: 0.452 Hom.: 26118

Bravo AF: 0.482

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		1.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs722571; hg19: chr19-12811379;