rs6969930

Variant names:

• chr7-128990259-T-C
• rs6969930
• NM_012470.4:c.1359-159A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-128990259-T-C
• chr7-128990259-T-A
• chr7-128990259-T-G

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.1359-159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 793,214 control chromosomes in the GnomAD database, including 144,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26625 hom., cov: 32)
  • Exomes 𝑓: 0.60 (118054 hom.)
• Consequence: TNPO3 NM_012470.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.105
• Publications: 21 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=-0.85).
• BP6: Variant 7-128990259-T-C is Benign according to our data. Variant chr7-128990259-T-C is described in ClinVar as Benign. ClinVar VariationId is 670777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.603 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.1359-159A>G		intron	N/A	NP_036602.1	Q9Y5L0-2
	TNPO3	NM_001382216.1		c.1359-57A>G		intron	N/A	NP_001369145.1	C9J7E5
	TNPO3	NM_001382217.1		c.1440-159A>G		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.1359-159A>G		intron	N/A	ENSP00000265388.5	Q9Y5L0-2
	TNPO3	ENST00000471234.5	TSL:1	c.1359-159A>G		intron	N/A	ENSP00000418646.1	Q9Y5L0-5
	TNPO3	ENST00000482320.5	TSL:1	c.1161-159A>G		intron	N/A	ENSP00000420089.1	E9PFH4

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89558 AN: 151918 Hom.: 26598 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.604 AC: 387431 AN: 641178 Hom.: 118054 AF XY: 0.605 AC XY: 206449 AN XY: 341130

African (AFR) AF: 0.574 AC: 9534 AN: 16598

American (AMR) AF: 0.540 AC: 16800 AN: 31090

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 13710 AN: 19282

East Asian (EAS) AF: 0.484 AC: 16590 AN: 34286

South Asian (SAS) AF: 0.626 AC: 39925 AN: 63738

European-Finnish (FIN) AF: 0.628 AC: 25050 AN: 39898

Middle Eastern (MID) AF: 0.621 AC: 2488 AN: 4006

European-Non Finnish (NFE) AF: 0.609 AC: 243310 AN: 399276

Other (OTH) AF: 0.607 AC: 20024 AN: 33004

GnomAD4 genome AF: 0.590 AC: 89632 AN: 152036 Hom.: 26625 Cov.: 32 AF XY: 0.587 AC XY: 43658 AN XY: 74324

African (AFR) AF: 0.575 AC: 23851 AN: 41472

American (AMR) AF: 0.525 AC: 8017 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2495 AN: 3470

East Asian (EAS) AF: 0.475 AC: 2458 AN: 5172

South Asian (SAS) AF: 0.619 AC: 2985 AN: 4822

European-Finnish (FIN) AF: 0.617 AC: 6517 AN: 10560

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41292 AN: 67968

Other (OTH) AF: 0.602 AC: 1270 AN: 2108

Alfa AF: 0.595 Hom.: 5210

Bravo AF: 0.584

Asia WGS AF: 0.537 AC: 1868 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.70
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6969930; hg19: chr7-128630313; COSMIC: COSV55288760;