chr7-129026771-A-G

Variant names:

• chr7-129026771-A-G
• rs34381587
• NM_012470.4:c.121-8614T>C

Variant summary

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

The NM_001382216.1(TNPO3):​c.121-8614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,138 control chromosomes in the GnomAD database, including 862 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 0.090 (862 hom., cov: 30)
• Consequence: TNPO3 NM_001382216.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382216.1. 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.121-8614T>C		intron	N/A	NP_036602.1
	TNPO3	NM_001382216.1		c.121-8614T>C		intron	N/A	NP_001369145.1
	TNPO3	NM_001382217.1		c.121-8614T>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.121-8614T>C		intron	N/A	ENSP00000265388.5
	TNPO3	ENST00000471234.5	TSL:1	c.121-8614T>C		intron	N/A	ENSP00000418646.1
	TNPO3	ENST00000482320.5	TSL:1	c.-78-8614T>C		intron	N/A	ENSP00000420089.1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13746 AN: 152020 Hom.: 865 Cov.: 30

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0903 AC: 13740 AN: 152138 Hom.: 862 Cov.: 30 AF XY: 0.0930 AC XY: 6918 AN XY: 74384

African (AFR) AF: 0.0243 AC: 1009 AN: 41502

American (AMR) AF: 0.138 AC: 2112 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5176

South Asian (SAS) AF: 0.153 AC: 738 AN: 4822

European-Finnish (FIN) AF: 0.146 AC: 1539 AN: 10568

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7652 AN: 68002

Other (OTH) AF: 0.102 AC: 215 AN: 2110

Alfa AF: 0.111 Hom.: 136

Bravo AF: 0.0870

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		0.31
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: rs34381587; hg19: chr7-128666825;