rs17424179

chr7-129017941-G-A

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.321+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,613,082 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (83 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1073 hom.)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.185

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=-0.65).
• BP6: Variant 7-129017941-G-A is Benign according to our data. Variant chr7-129017941-G-A is described in ClinVar as [Benign]. Clinvar id is 260266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-129017941-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO3	NM_012470.4	c.321+16C>T		intron_variant		ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10	c.321+16C>T		intron_variant		1	NM_012470.4	P1

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 3999 AN: 152124 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0306 AC: 7666 AN: 250750 Hom.: 168 AF XY: 0.0334 AC XY: 4534 AN XY: 135552

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0491

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0499

Gnomad FIN exome AF: 0.0293

Gnomad NFE exome AF: 0.0365

Gnomad OTH exome AF: 0.0398

GnomAD4 exome AF: 0.0351 AC: 51347 AN: 1460840 Hom.: 1073 Cov.: 31 AF XY: 0.0359 AC XY: 26089 AN XY: 726782

Gnomad4 AFR exome AF: 0.00550

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.0465

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0497

Gnomad4 FIN exome AF: 0.0282

Gnomad4 NFE exome AF: 0.0369

Gnomad4 OTH exome AF: 0.0331

GnomAD4 genome AF: 0.0263 AC: 3997 AN: 152242 Hom.: 83 Cov.: 32 AF XY: 0.0262 AC XY: 1951 AN XY: 74434

Gnomad4 AFR AF: 0.00631

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0369

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0358 Hom.: 103

Bravo AF: 0.0244

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	9.9
Dann	Benign	0.73

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: rs17424179; hg19: chr7-128657995;