chr19-12700565-T-C

Position:

• chr19-12700565-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO2	NM_001382241.1	c.*699A>G		3_prime_UTR_variant	26/26	ENST00000425528.6	NP_001369170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO2	ENST00000425528.6	c.*699A>G		3_prime_UTR_variant	26/26	5	NM_001382241.1	ENSP00000407182
TNPO2	ENST00000356861.9	c.*699A>G		3_prime_UTR_variant	25/25	1		ENSP00000349321	P1
TNPO2	ENST00000450764.6	c.*699A>G		3_prime_UTR_variant	24/24	1		ENSP00000397379	P1

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.417

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.484

Alfa AF: 0.447 Hom.: 20327

Bravo AF: 0.482

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.64
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

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: rs722571; hg19: chr19-12811379;