7-128959343-C-T

Variant names:

• chr7-128959343-C-T
• rs10229001
• NM_012470.4:c.2712-2028G>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.2712-2028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,022 control chromosomes in the GnomAD database, including 26,918 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 0.59 (26918 hom., cov: 32)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 19 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 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.2712-2028G>A		intron	N/A	NP_036602.1	Q9Y5L0-2
	TNPO3	NM_001382216.1		c.2814-2028G>A		intron	N/A	NP_001369145.1	C9J7E5
	TNPO3	NM_001382217.1		c.2793-2028G>A		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.2712-2028G>A		intron	N/A	ENSP00000265388.5	Q9Y5L0-2
	TNPO3	ENST00000471234.5	TSL:1	c.2520-2028G>A		intron	N/A	ENSP00000418646.1	Q9Y5L0-5
	TNPO3	ENST00000482320.5	TSL:1	c.2514-2028G>A		intron	N/A	ENSP00000420089.1	E9PFH4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90050 AN: 151904 Hom.: 26892 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.593 AC: 90123 AN: 152022 Hom.: 26918 Cov.: 32 AF XY: 0.590 AC XY: 43871 AN XY: 74310

African (AFR) AF: 0.577 AC: 23927 AN: 41450

American (AMR) AF: 0.530 AC: 8095 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2496 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2455 AN: 5160

South Asian (SAS) AF: 0.618 AC: 2974 AN: 4810

European-Finnish (FIN) AF: 0.623 AC: 6583 AN: 10574

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

European-Non Finnish (NFE) AF: 0.611 AC: 41554 AN: 67956

Other (OTH) AF: 0.605 AC: 1279 AN: 2114

Alfa AF: 0.607 Hom.: 12288

Bravo AF: 0.587

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.11
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: rs10229001; hg19: chr7-128599397;