rs201210726

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_012470.4(TNPO3):​c.2625C>T​(p.Ser875=) 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

2

Clinical Significance

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

Conservation

PhyloP100: -0.305
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 283447.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.305 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome 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 gnomad4_exome. There are 75 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNPO3NM_012470.4 linkuse as main transcriptc.2625C>T p.Ser875= synonymous_variant 21/23 ENST00000265388.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNPO3ENST00000265388.10 linkuse as main transcriptc.2625C>T p.Ser875= synonymous_variant 21/231 NM_012470.4 P1Q9Y5L0-2

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152180
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.000179
AC:
45
AN:
251436
Hom.:
0
AF XY:
0.000191
AC XY:
26
AN XY:
135894
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 SAS 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.:
0
Cov.:
31
AF XY:
0.000103
AC XY:
75
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000850
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000918
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000965
Hom.:
0
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
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Sep 06, 2016- -
Autosomal dominant limb-girdle muscular dystrophy type 1F Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 11, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
8.9
DANN
Benign
0.83
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201210726; hg19: chr7-128607420; API