7-129028456-T-G

Variant names:

• chr7-129028456-T-G
• rs10239340
• NM_012470.4:c.121-10299A>C

Variant summary

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

The ENST00000265388.10(TNPO3):​c.121-10299A>C 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 151,898 control chromosomes in the GnomAD database, including 26,901 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 (26901 hom., cov: 32)
• Consequence: TNPO3 ENST00000265388.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 30 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 (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265388.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	NM_012470.4	MANE Select	c.121-10299A>C		intron	N/A	NP_036602.1
	TNPO3	NM_001382216.1		c.121-10299A>C		intron	N/A	NP_001369145.1
	TNPO3	NM_001382217.1		c.121-10299A>C		intron	N/A	NP_001369146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	ENST00000265388.10	TSL:1 MANE Select	c.121-10299A>C		intron	N/A	ENSP00000265388.5
	TNPO3	ENST00000471234.5	TSL:1	c.121-10299A>C		intron	N/A	ENSP00000418646.1
	TNPO3	ENST00000482320.5	TSL:1	c.-78-10299A>C		intron	N/A	ENSP00000420089.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90030 AN: 151780 Hom.: 26876 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.593 AC: 90102 AN: 151898 Hom.: 26901 Cov.: 32 AF XY: 0.591 AC XY: 43856 AN XY: 74210

African (AFR) AF: 0.576 AC: 23867 AN: 41416

American (AMR) AF: 0.531 AC: 8107 AN: 15272

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

East Asian (EAS) AF: 0.477 AC: 2455 AN: 5146

South Asian (SAS) AF: 0.619 AC: 2981 AN: 4816

European-Finnish (FIN) AF: 0.623 AC: 6556 AN: 10518

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41595 AN: 67950

Other (OTH) AF: 0.607 AC: 1283 AN: 2112

Alfa AF: 0.606 Hom.: 85122

Bravo AF: 0.587

Asia WGS AF: 0.541 AC: 1882 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	3.2
DANN	Benign	0.80
PhyloP100		-0.067
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10239340; hg19: chr7-128668510;