7-129015864-C-T

Position:

• chr7-129015864-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012470.4(TNPO3):​c.396-729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,616 control chromosomes in the GnomAD database, including 25,710 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25710 hom., cov: 30)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO3	NM_012470.4	c.396-729G>A		intron_variant		ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10	c.396-729G>A		intron_variant		1	NM_012470.4	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87796 AN: 151496 Hom.: 25699 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.579 AC: 87847 AN: 151616 Hom.: 25710 Cov.: 30 AF XY: 0.577 AC XY: 42775 AN XY: 74074

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.597

Alfa AF: 0.613 Hom.: 15979

Bravo AF: 0.571

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.88

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: rs6965542; hg19: chr7-128655918;