7-128981150-A-G

Variant names:

• chr7-128981150-A-G
• rs7789423
• NM_012470.4:c.1859+1098T>C

Variant summary

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

The NM_012470.4(TNPO3):​c.1859+1098T>C 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 152,026 control chromosomes in the GnomAD database, including 31,168 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 (31168 hom., cov: 32)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.1859+1098T>C		intron_variant	Intron 14 of 22	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.1859+1098T>C		intron_variant	Intron 14 of 22	1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96778 AN: 151906 Hom.: 31140 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.637 AC: 96851 AN: 152026 Hom.: 31168 Cov.: 32 AF XY: 0.638 AC XY: 47427 AN XY: 74306

African (AFR) AF: 0.594 AC: 24608 AN: 41446

American (AMR) AF: 0.564 AC: 8616 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2902 AN: 5168

South Asian (SAS) AF: 0.689 AC: 3327 AN: 4828

European-Finnish (FIN) AF: 0.735 AC: 7762 AN: 10558

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44830 AN: 67976

Other (OTH) AF: 0.646 AC: 1362 AN: 2108

Alfa AF: 0.654 Hom.: 19183

Bravo AF: 0.623

Asia WGS AF: 0.629 AC: 2182 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.30
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: rs7789423; hg19: chr7-128621204;