7-128954671-C-T

Position:

• chr7-128954671-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.*746G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,840 control chromosomes in the GnomAD database, including 31,104 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 0.64 (31086 hom., cov: 29)
  • Exomes 𝑓: 0.65 (18 hom.)
• Consequence: TNPO3 NM_012470.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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]

TNPO3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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	Protein	UniProt
TNPO3	NM_012470.4	c.*746G>A		3_prime_UTR_variant	23/23	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388	c.*746G>A		3_prime_UTR_variant	23/23	1	NM_012470.4	ENSP00000265388.5
TNPO3	ENST00000627585	c.*746G>A		3_prime_UTR_variant	23/23	2		ENSP00000487231.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96573 AN: 151638 Hom.: 31058 Cov.: 29

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.655 AC: 55 AN: 84 Hom.: 18 Cov.: 0 AF XY: 0.661 AC XY: 41 AN XY: 62

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.637 AC: 96645 AN: 151756 Hom.: 31086 Cov.: 29 AF XY: 0.638 AC XY: 47298 AN XY: 74140

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.645

Alfa AF: 0.656 Hom.: 31818

Bravo AF: 0.623

Asia WGS AF: 0.630 AC: 2193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2280714; hg19: chr7-128594725;