chr7-128956751-C-T

Variant names:

• chr7-128956751-C-T
• rs12539741
• NM_012470.4:c.*31+473G>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.*31+473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 152,240 control chromosomes in the GnomAD database, including 857 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 (857 hom., cov: 32)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.*31+473G>A		intron_variant	Intron 22 of 22	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.*31+473G>A		intron_variant	Intron 22 of 22	1	NM_012470.4	ENSP00000265388.5
TNPO3	ENST00000471234.5	c.*31+473G>A		intron_variant	Intron 21 of 21	1		ENSP00000418646.1
TNPO3	ENST00000482320.5	c.*31+473G>A		intron_variant	Intron 23 of 23	1		ENSP00000420089.1
TNPO3	ENST00000627585.2	c.*31+473G>A		intron_variant	Intron 22 of 22	2		ENSP00000487231.1

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13726 AN: 152122 Hom.: 860 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0901 AC: 13720 AN: 152240 Hom.: 857 Cov.: 32 AF XY: 0.0927 AC XY: 6902 AN XY: 74426

African (AFR) AF: 0.0243 AC: 1010 AN: 41562

American (AMR) AF: 0.138 AC: 2105 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5192

South Asian (SAS) AF: 0.152 AC: 735 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1536 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7644 AN: 68002

Other (OTH) AF: 0.102 AC: 214 AN: 2108

Alfa AF: 0.108 Hom.: 141

Bravo AF: 0.0869

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.54
PhyloP100		0.17
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: rs12539741; hg19: chr7-128596805;