19-12703730-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001382241.1(TNPO2):c.2094T>C(p.His698=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,608,662 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (101 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (119 hom.)
• Consequence: TNPO2 NM_001382241.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.34

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-12703730-A-G is Benign according to our data. Variant chr19-12703730-A-G is described in ClinVar as [Benign]. Clinvar id is 775408.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO2	NM_001382241.1	c.2094T>C	p.His698=	synonymous_variant	19/26	ENST00000425528.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO2	ENST00000425528.6	c.2094T>C	p.His698=	synonymous_variant	19/26	5	NM_001382241.1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3158 AN: 152158 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00489 AC: 1171 AN: 239570 Hom.: 46 AF XY: 0.00375 AC XY: 487 AN XY: 130034

Gnomad AFR exome AF: 0.0689

Gnomad AMR exome AF: 0.00322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000369

Gnomad OTH exome AF: 0.00290

GnomAD4 exome AF: 0.00225 AC: 3283 AN: 1456386 Hom.: 119 Cov.: 31 AF XY: 0.00196 AC XY: 1420 AN XY: 724010

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000937

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00510

GnomAD4 genome AF: 0.0209 AC: 3175 AN: 152276 Hom.: 101 Cov.: 32 AF XY: 0.0194 AC XY: 1442 AN XY: 74464

Gnomad4 AFR AF: 0.0714

Gnomad4 AMR AF: 0.00896

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00871 Hom.: 21

Bravo AF: 0.0234

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.43
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16978633; hg19: chr19-12814544;