rs17414687
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_015571.4(SENP6):c.1119G>A(p.Ala373Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,612,104 control chromosomes in the GnomAD database, including 93,170 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.26 ( 6241 hom., cov: 32)
Exomes 𝑓: 0.33 ( 86929 hom. )
Consequence
SENP6
NM_015571.4 synonymous
NM_015571.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.472
Genes affected
SENP6 (HGNC:20944): (SUMO specific peptidase 6) Ubiquitin-like molecules (UBLs), such as SUMO1 (UBL1; MIM 601912), are structurally related to ubiquitin (MIM 191339) and can be ligated to target proteins in a similar manner as ubiquitin. However, covalent attachment of UBLs does not result in degradation of the modified proteins. SUMO1 modification is implicated in the targeting of RANGAP1 (MIM 602362) to the nuclear pore complex, as well as in stabilization of I-kappa-B-alpha (NFKBIA; MIM 164008) from degradation by the 26S proteasome. Like ubiquitin, UBLs are synthesized as precursor proteins, with 1 or more amino acids following the C-terminal glycine-glycine residues of the mature UBL protein. Thus, the tail sequences of the UBL precursors need to be removed by UBL-specific proteases, such as SENP6, prior to their conjugation to target proteins (Kim et al., 2000 [PubMed 10799485]). SENPs also display isopeptidase activity for deconjugation of SUMO-conjugated substrates (Lima and Reverter, 2008 [PubMed 18799455]).[supplied by OMIM, Jun 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=-0.472 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SENP6 | NM_015571.4 | c.1119G>A | p.Ala373Ala | synonymous_variant | 10/24 | ENST00000447266.7 | NP_056386.2 | |
SENP6 | NM_001100409.3 | c.1098G>A | p.Ala366Ala | synonymous_variant | 9/23 | NP_001093879.1 | ||
SENP6 | NM_001304792.2 | c.1098G>A | p.Ala366Ala | synonymous_variant | 9/15 | NP_001291721.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SENP6 | ENST00000447266.7 | c.1119G>A | p.Ala373Ala | synonymous_variant | 10/24 | 1 | NM_015571.4 | ENSP00000402527.2 |
Frequencies
GnomAD3 genomes AF: 0.264 AC: 40152AN: 152010Hom.: 6243 Cov.: 32
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GnomAD3 exomes AF: 0.269 AC: 67049AN: 249210Hom.: 10651 AF XY: 0.279 AC XY: 37718AN XY: 135198
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GnomAD4 exome AF: 0.335 AC: 488794AN: 1459976Hom.: 86929 Cov.: 33 AF XY: 0.334 AC XY: 242414AN XY: 726426
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GnomAD4 genome AF: 0.264 AC: 40143AN: 152128Hom.: 6241 Cov.: 32 AF XY: 0.258 AC XY: 19155AN XY: 74378
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Not reported inComputational 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