chr7-128954671-C-T

Variant names:

• chr7-128954671-C-T
• rs2280714
• NM_012470.4:c.*746G>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.*746G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,840 control chromosomes in the GnomAD database, including 31,104 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 0.64 (31086 hom., cov: 29)
  • Exomes 𝑓: 0.65 (18 hom.)
• Consequence: TNPO3 NM_012470.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730
• Publications: 90 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	NM_012470.4	MANE Select	c.*746G>A		3_prime_UTR	Exon 23 of 23	NP_036602.1
	TNPO3	NR_034053.3		n.4020G>A		non_coding_transcript_exon	Exon 24 of 24
	TNPO3	NR_167911.1		n.4107G>A		non_coding_transcript_exon	Exon 25 of 25

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	ENST00000265388.10	TSL:1 MANE Select	c.*746G>A		3_prime_UTR	Exon 23 of 23	ENSP00000265388.5
	TNPO3	ENST00000627585.2	TSL:2	c.*746G>A		3_prime_UTR	Exon 23 of 23	ENSP00000487231.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96573 AN: 151638 Hom.: 31058 Cov.: 29

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.648

GnomAD4 exome AF: 0.655 AC: 55 AN: 84 Hom.: 18 Cov.: 0 AF XY: 0.661 AC XY: 41 AN XY: 62

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 52 AN: 78

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.637 AC: 96645 AN: 151756 Hom.: 31086 Cov.: 29 AF XY: 0.638 AC XY: 47298 AN XY: 74140

African (AFR) AF: 0.593 AC: 24527 AN: 41342

American (AMR) AF: 0.564 AC: 8598 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2613 AN: 3464

East Asian (EAS) AF: 0.559 AC: 2876 AN: 5142

South Asian (SAS) AF: 0.690 AC: 3311 AN: 4802

European-Finnish (FIN) AF: 0.735 AC: 7745 AN: 10536

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44802 AN: 67932

Other (OTH) AF: 0.645 AC: 1354 AN: 2098

Alfa AF: 0.651 Hom.: 41041

Bravo AF: 0.623

Asia WGS AF: 0.630 AC: 2193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2280714; hg19: chr7-128594725;