7-128967366-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_012470.4(TNPO3):c.2625C>T(p.Ser875Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 0 hom. )

Consequence

TNPO3
NM_012470.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.305

Publications

2 publications found

Variant links:

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

TNPO3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 7-128967366-G-A is Benign according to our data. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447. Variant chr7-128967366-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 283447.

BP7

Synonymous conserved (PhyloP=-0.305 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000972 (142/1461510) while in subpopulation AMR AF = 0.00085 (38/44722). AF 95% confidence interval is 0.000636. There are 0 homozygotes in GnomAdExome4. There are 75 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4 link	c.2625C>T	p.Ser875Ser	synonymous_variant	Exon 21 of 23	ENST00000265388.10	NP_036602.1	Q9Y5L0-2A0A024R794B3KMX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10 link	c.2625C>T	p.Ser875Ser	synonymous_variant	Exon 21 of 23	1	NM_012470.4	ENSP00000265388.5		Q9Y5L0-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000179

AC:

AN:

251436

AF XY:

0.000191

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000972

AC:

142

AN:

1461510

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.000850

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000918

AC:

102

AN:

1111698

Other (OTH)

AF:

0.0000331

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41554

American (AMR)

AF:

0.000523

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.000125

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 06, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant limb-girdle muscular dystrophy type 1F

Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.9

(source)

DANN

Benign

0.83

PhyloP100

-0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over