chr7-99173777-T-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001145715.3(KPNA7):c.1482A>G(p.Gln494=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000568 in 1,549,600 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
KPNA7
NM_001145715.3 synonymous
NM_001145715.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.997
Genes affected
KPNA7 (HGNC:21839): (karyopherin subunit alpha 7) The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import, but exhibits different nuclear localization signal binding specificity compared to other members of the family. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 7-99173777-T-C is Benign according to our data. Variant chr7-99173777-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1159089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.997 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPNA7 | NM_001145715.3 | c.1482A>G | p.Gln494= | synonymous_variant | 11/11 | ENST00000327442.7 | |
KPNA7 | XM_011516215.3 | c.1563A>G | p.Gln521= | synonymous_variant | 11/11 | ||
KPNA7 | XM_017012211.2 | c.1545+4143A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPNA7 | ENST00000327442.7 | c.1482A>G | p.Gln494= | synonymous_variant | 11/11 | 1 | NM_001145715.3 | P1 | |
KPNA7 | ENST00000681060.1 | c.1482A>G | p.Gln494= | synonymous_variant | 11/11 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000317 AC: 5AN: 157948Hom.: 0 AF XY: 0.0000600 AC XY: 5AN XY: 83280
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GnomAD4 exome AF: 0.0000544 AC: 76AN: 1397414Hom.: 0 Cov.: 28 AF XY: 0.0000667 AC XY: 46AN XY: 689362
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74342
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
KPNA7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at