7-128957750-C-T

Position:

• chr7-128957750-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.2712-435G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,976 control chromosomes in the GnomAD database, including 18,298 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 (18298 hom., cov: 32)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNPO3	NM_012470.4	c.2712-435G>A		intron_variant		ENST00000265388.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNPO3	ENST00000265388.10	c.2712-435G>A		intron_variant		1	NM_012470.4	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74117 AN: 151858 Hom.: 18283 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.488 AC: 74170 AN: 151976 Hom.: 18298 Cov.: 32 AF XY: 0.483 AC XY: 35907 AN XY: 74280

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.498

Alfa AF: 0.500 Hom.: 25054

Bravo AF: 0.485

Asia WGS AF: 0.473 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.8
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17166351; hg19: chr7-128597804;