7-129015864-C-T

Variant names:

• chr7-129015864-C-T
• rs6965542
• NM_012470.4:c.396-729G>A

Variant summary

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

The NM_012470.4(TNPO3):​c.396-729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,616 control chromosomes in the GnomAD database, including 25,710 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 0.58 (25710 hom., cov: 30)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 21 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):

• autosomal dominant limb-girdle muscular dystrophy type 1F

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.396-729G>A		intron_variant	Intron 3 of 22	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.396-729G>A		intron_variant	Intron 3 of 22	1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87796 AN: 151496 Hom.: 25699 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.579 AC: 87847 AN: 151616 Hom.: 25710 Cov.: 30 AF XY: 0.577 AC XY: 42775 AN XY: 74074

African (AFR) AF: 0.530 AC: 21878 AN: 41304

American (AMR) AF: 0.525 AC: 8001 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2503 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2455 AN: 5148

South Asian (SAS) AF: 0.617 AC: 2960 AN: 4794

European-Finnish (FIN) AF: 0.623 AC: 6533 AN: 10484

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41506 AN: 67892

Other (OTH) AF: 0.597 AC: 1251 AN: 2094

Alfa AF: 0.611 Hom.: 22902

Bravo AF: 0.571

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.88
PhyloP100		-1.0
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: rs6965542; hg19: chr7-128655918;