7-128983043-T-C

Variant names:

• chr7-128983043-T-C
• rs6948928
• NM_012470.4:c.1783-719A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012470.4(TNPO3):​c.1783-719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,972 control chromosomes in the GnomAD database, including 31,140 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 (31140 hom., cov: 31)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1F

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012470.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	NM_012470.4	MANE Select	c.1783-719A>G		intron	N/A	NP_036602.1	Q9Y5L0-2
	TNPO3	NM_001382216.1		c.1885-719A>G		intron	N/A	NP_001369145.1	C9J7E5
	TNPO3	NM_001382217.1		c.1864-719A>G		intron	N/A	NP_001369146.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	ENST00000265388.10	TSL:1 MANE Select	c.1783-719A>G		intron	N/A	ENSP00000265388.5	Q9Y5L0-2
	TNPO3	ENST00000471234.5	TSL:1	c.1591-719A>G		intron	N/A	ENSP00000418646.1	Q9Y5L0-5
	TNPO3	ENST00000482320.5	TSL:1	c.1585-719A>G		intron	N/A	ENSP00000420089.1	E9PFH4

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96723 AN: 151854 Hom.: 31113 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.637 AC: 96794 AN: 151972 Hom.: 31140 Cov.: 31 AF XY: 0.638 AC XY: 47376 AN XY: 74262

African (AFR) AF: 0.594 AC: 24588 AN: 41426

American (AMR) AF: 0.563 AC: 8602 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2622 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2911 AN: 5176

South Asian (SAS) AF: 0.690 AC: 3322 AN: 4816

European-Finnish (FIN) AF: 0.735 AC: 7744 AN: 10538

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44823 AN: 67966

Other (OTH) AF: 0.647 AC: 1366 AN: 2110

Alfa AF: 0.643 Hom.: 4346

Bravo AF: 0.623

Asia WGS AF: 0.629 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6948928; hg19: chr7-128623097;