rs112438598

Positions:

• chr7-128975947-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012470.4(TNPO3):​c.2062-12T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,571,134 control chromosomes in the GnomAD database, including 1,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (655 hom., cov: 32)
  • Exomes 𝑓: 0.026 (914 hom.)
• Consequence: TNPO3 NM_012470.4 intron
• Scores: Splicing: ADA: 0.003724
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.534

Genes affected

TNPO3 (HGNC:17103): (transportin 3) The protein encoded by this gene is a nuclear import receptor for serine/arginine-rich (SR) proteins such as the splicing factors SFRS1 and SFRS2. The encoded protein has also been shown to be involved in HIV-1 infection, apparently through interaction with the HIV-1 capsid protein. Several protein-coding and non-coding transcript variants have been found for this gene. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-128975947-A-C is Benign according to our data. Variant chr7-128975947-A-C is described in ClinVar as [Benign]. Clinvar id is 260261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128975947-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.2062-12T>G		intron_variant		ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.2062-12T>G		intron_variant		1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9784 AN: 152174 Hom.: 656 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0279 AC: 6968 AN: 250162 Hom.: 297 AF XY: 0.0241 AC XY: 3261 AN XY: 135186

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.0148

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00379

Gnomad FIN exome AF: 0.0335

Gnomad NFE exome AF: 0.0232

Gnomad OTH exome AF: 0.0209

GnomAD4 exome AF: 0.0263 AC: 37300 AN: 1418842 Hom.: 914 Cov.: 24 AF XY: 0.0250 AC XY: 17696 AN XY: 708344

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.0162

Gnomad4 ASJ exome AF: 0.00488

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00431

Gnomad4 FIN exome AF: 0.0354

Gnomad4 NFE exome AF: 0.0250

Gnomad4 OTH exome AF: 0.0284

GnomAD4 genome AF: 0.0643 AC: 9792 AN: 152292 Hom.: 655 Cov.: 32 AF XY: 0.0622 AC XY: 4634 AN XY: 74472

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0376 Hom.: 53

Bravo AF: 0.0672

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 23, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Autosomal dominant limb-girdle muscular dystrophy type 1F Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0037
dbscSNV1_RF	Benign	0.078
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: rs112438598; hg19: chr7-128616001;