chr7-128958471-C-G

Position:

• chr7-128958471-C-G

Variant summary

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

The NM_012470.4(TNPO3):​c.2712-1156G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,050 control chromosomes in the GnomAD database, including 2,778 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 0.17 (2778 hom., cov: 31)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.2712-1156G>C		intron_variant		ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.2712-1156G>C		intron_variant		1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26490 AN: 151932 Hom.: 2763 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.175 AC: 26537 AN: 152050 Hom.: 2778 Cov.: 31 AF XY: 0.178 AC XY: 13205 AN XY: 74320

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.179

Alfa AF: 0.169 Hom.: 271

Bravo AF: 0.187

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.37

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: rs6966125; hg19: chr7-128598525;