7-128957533-T-G

Position:

• chr7-128957533-T-G

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.2712-218A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,978 control chromosomes in the GnomAD database, including 31,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.64 (31164 hom., cov: 31)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.410

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=-0.87).
• BP6: Variant 7-128957533-T-G is Benign according to our data. Variant chr7-128957533-T-G is described in ClinVar as [Benign]. Clinvar id is 670796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO3	NM_012470.4	c.2712-218A>C		intron_variant		ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10	c.2712-218A>C		intron_variant		1	NM_012470.4	P1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96746 AN: 151860 Hom.: 31137 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.650

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.637 AC: 96817 AN: 151978 Hom.: 31164 Cov.: 31 AF XY: 0.638 AC XY: 47396 AN XY: 74278

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.647

Alfa AF: 0.659 Hom.: 31045

Bravo AF: 0.623

Asia WGS AF: 0.630 AC: 2193 AN: 3478

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	-0.87
CADD	Benign	6.0
DANN	Benign	0.33

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: rs10236569; hg19: chr7-128597587;