7-128965913-C-T

Position:

• chr7-128965913-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.2711+1367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,816 control chromosomes in the GnomAD database, including 18,118 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 0.49 (18118 hom., cov: 31)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.2711+1367G>A		intron_variant		ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.2711+1367G>A		intron_variant		1	NM_012470.4	ENSP00000265388	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73705 AN: 151698 Hom.: 18101 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.486 AC: 73762 AN: 151816 Hom.: 18118 Cov.: 31 AF XY: 0.482 AC XY: 35727 AN XY: 74194

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.490

Alfa AF: 0.482 Hom.: 2358

Bravo AF: 0.482

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.67

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: rs4731535; hg19: chr7-128605967;