7-128965913-C-T

Variant names:

• chr7-128965913-C-T
• rs4731535
• NM_012470.4:c.2711+1367G>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.2711+1367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,816 control chromosomes in the GnomAD database, including 18,118 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 (18118 hom., cov: 31)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 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.2711+1367G>A		intron	N/A	NP_036602.1
	TNPO3	NM_001382216.1		c.2813+1367G>A		intron	N/A	NP_001369145.1
	TNPO3	NM_001382217.1		c.2792+1367G>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.2711+1367G>A		intron	N/A	ENSP00000265388.5
	TNPO3	ENST00000471234.5	TSL:1	c.2519+1367G>A		intron	N/A	ENSP00000418646.1
	TNPO3	ENST00000482320.5	TSL:1	c.2513+1367G>A		intron	N/A	ENSP00000420089.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73705 AN: 151698 Hom.: 18101 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.486 AC: 73762 AN: 151816 Hom.: 18118 Cov.: 31 AF XY: 0.482 AC XY: 35727 AN XY: 74194

African (AFR) AF: 0.505 AC: 20888 AN: 41390

American (AMR) AF: 0.382 AC: 5825 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2099 AN: 3464

East Asian (EAS) AF: 0.474 AC: 2451 AN: 5170

South Asian (SAS) AF: 0.462 AC: 2225 AN: 4812

European-Finnish (FIN) AF: 0.474 AC: 4980 AN: 10516

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33583 AN: 67898

Other (OTH) AF: 0.490 AC: 1033 AN: 2108

Alfa AF: 0.483 Hom.: 5395

Bravo AF: 0.482

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.67
PhyloP100		-0.57
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: rs4731535; hg19: chr7-128605967;