rs17424179

Variant names:

• chr7-129017941-G-A
• rs17424179
• NM_012470.4:c.321+16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012470.4(TNPO3):​c.321+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,613,082 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (83 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1073 hom.)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.185
• 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):

• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1F

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 7-129017941-G-A is Benign according to our data. Variant chr7-129017941-G-A is described in ClinVar as Benign. ClinVar VariationId is 260266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0571 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	NM_012470.4	MANE Select	c.321+16C>T		intron	N/A	NP_036602.1	Q9Y5L0-2
	TNPO3	NM_001382216.1		c.321+16C>T		intron	N/A	NP_001369145.1	C9J7E5
	TNPO3	NM_001382217.1		c.321+16C>T		intron	N/A	NP_001369146.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	ENST00000265388.10	TSL:1 MANE Select	c.321+16C>T		intron	N/A	ENSP00000265388.5	Q9Y5L0-2
	TNPO3	ENST00000471234.5	TSL:1	c.321+16C>T		intron	N/A	ENSP00000418646.1	Q9Y5L0-5
	TNPO3	ENST00000482320.5	TSL:1	c.123+16C>T		intron	N/A	ENSP00000420089.1	E9PFH4

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 3999 AN: 152124 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0268

GnomAD2 exomes AF: 0.0306 AC: 7666 AN: 250750 AF XY: 0.0334

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0491

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0293

Gnomad NFE exome AF: 0.0365

Gnomad OTH exome AF: 0.0398

GnomAD4 exome AF: 0.0351 AC: 51347 AN: 1460840 Hom.: 1073 Cov.: 31 AF XY: 0.0359 AC XY: 26089 AN XY: 726782

African (AFR) AF: 0.00550 AC: 184 AN: 33442

American (AMR) AF: 0.0182 AC: 812 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 1215 AN: 26120

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39684

South Asian (SAS) AF: 0.0497 AC: 4285 AN: 86184

European-Finnish (FIN) AF: 0.0282 AC: 1505 AN: 53402

Middle Eastern (MID) AF: 0.0625 AC: 360 AN: 5764

European-Non Finnish (NFE) AF: 0.0369 AC: 40984 AN: 1111214

Other (OTH) AF: 0.0331 AC: 1996 AN: 60352

GnomAD4 genome AF: 0.0263 AC: 3997 AN: 152242 Hom.: 83 Cov.: 32 AF XY: 0.0262 AC XY: 1951 AN XY: 74434

African (AFR) AF: 0.00631 AC: 262 AN: 41548

American (AMR) AF: 0.0212 AC: 324 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4822

European-Finnish (FIN) AF: 0.0326 AC: 345 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0369 AC: 2508 AN: 68018

Other (OTH) AF: 0.0265 AC: 56 AN: 2114

Alfa AF: 0.0340 Hom.: 216

Bravo AF: 0.0244

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Autosomal dominant limb-girdle muscular dystrophy type 1F (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.9
DANN	Benign	0.73
PhyloP100		0.18
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: rs17424179; hg19: chr7-128657995;