rs2293493
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_012470.4(TNPO3):c.2205C>T(p.Leu735=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 1,613,834 control chromosomes in the GnomAD database, including 2,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.042 ( 201 hom., cov: 32)
Exomes 𝑓: 0.048 ( 2032 hom. )
Consequence
TNPO3
NM_012470.4 synonymous
NM_012470.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.981
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
Variant 7-128974936-G-A is Benign according to our data. Variant chr7-128974936-G-A is described in ClinVar as [Benign]. Clinvar id is 260262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128974936-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.981 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNPO3 | NM_012470.4 | c.2205C>T | p.Leu735= | synonymous_variant | 18/23 | ENST00000265388.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNPO3 | ENST00000265388.10 | c.2205C>T | p.Leu735= | synonymous_variant | 18/23 | 1 | NM_012470.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0415 AC: 6320AN: 152136Hom.: 200 Cov.: 32
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GnomAD3 exomes AF: 0.0514 AC: 12937AN: 251454Hom.: 433 AF XY: 0.0540 AC XY: 7343AN XY: 135900
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GnomAD4 exome AF: 0.0478 AC: 69838AN: 1461580Hom.: 2032 Cov.: 30 AF XY: 0.0488 AC XY: 35449AN XY: 727118
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GnomAD4 genome ? AF: 0.0415 AC: 6319AN: 152254Hom.: 201 Cov.: 32 AF XY: 0.0455 AC XY: 3387AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal dominant limb-girdle muscular dystrophy type 1F Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at