7-128990259-T-C

Position:

• chr7-128990259-T-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.1359-159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 793,214 control chromosomes in the GnomAD database, including 144,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26625 hom., cov: 32)
  • Exomes 𝑓: 0.60 (118054 hom.)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.105

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=-0.85).
• BP6: Variant 7-128990259-T-C is Benign according to our data. Variant chr7-128990259-T-C is described in ClinVar as [Benign]. Clinvar id is 670777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.1359-159A>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.1359-159A>G		intron_variant		1	NM_012470.4	ENSP00000265388	P1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89558 AN: 151918 Hom.: 26598 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.604 AC: 387431 AN: 641178 Hom.: 118054 AF XY: 0.605 AC XY: 206449 AN XY: 341130

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.711

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 0.609

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.590 AC: 89632 AN: 152036 Hom.: 26625 Cov.: 32 AF XY: 0.587 AC XY: 43658 AN XY: 74324

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.602

Alfa AF: 0.601 Hom.: 4338

Bravo AF: 0.584

Asia WGS AF: 0.537 AC: 1868 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6969930; hg19: chr7-128630313; COSMIC: COSV55288760;