rs6966125

Variant names:

• chr7-128958471-C-G
• rs6966125
• NM_012470.4:c.2712-1156G>C

Variant summary

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

The NM_012470.4(TNPO3):​c.2712-1156G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,050 control chromosomes in the GnomAD database, including 2,778 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 0.17 (2778 hom., cov: 31)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.2712-1156G>C		intron_variant	Intron 21 of 22	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.2712-1156G>C		intron_variant	Intron 21 of 22	1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26490 AN: 151932 Hom.: 2763 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.175 AC: 26537 AN: 152050 Hom.: 2778 Cov.: 31 AF XY: 0.178 AC XY: 13205 AN XY: 74320

African (AFR) AF: 0.143 AC: 5939 AN: 41490

American (AMR) AF: 0.297 AC: 4532 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2218 AN: 5170

South Asian (SAS) AF: 0.138 AC: 663 AN: 4814

European-Finnish (FIN) AF: 0.137 AC: 1448 AN: 10566

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10763 AN: 67964

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.169 Hom.: 271

Bravo AF: 0.187

Asia WGS AF: 0.264 AC: 920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.37
PhyloP100		-0.43
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: rs6966125; hg19: chr7-128598525;