rs1328323
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_021738.3(SVIL):āc.1773A>Gā(p.Lys591=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,678 control chromosomes in the GnomAD database, including 139,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.39 ( 12024 hom., cov: 32)
Exomes š: 0.41 ( 127009 hom. )
Consequence
SVIL
NM_021738.3 synonymous
NM_021738.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.04
Genes affected
SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 10-29532594-T-C is Benign according to our data. Variant chr10-29532594-T-C is described in ClinVar as [Benign]. Clinvar id is 1260962.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SVIL | NM_021738.3 | c.1773A>G | p.Lys591= | synonymous_variant | 8/38 | ENST00000355867.9 | |
SVIL | NM_001323599.2 | c.909-422A>G | intron_variant | ||||
SVIL | NM_001323600.1 | c.828-1306A>G | intron_variant | ||||
SVIL | NM_003174.3 | c.828-1306A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SVIL | ENST00000355867.9 | c.1773A>G | p.Lys591= | synonymous_variant | 8/38 | 1 | NM_021738.3 | A2 | |
SVIL | ENST00000375400.7 | c.828-1306A>G | intron_variant | 1 | P2 | ||||
SVIL | ENST00000375398.6 | c.1773A>G | p.Lys591= | synonymous_variant | 8/37 | 5 | A2 | ||
SVIL | ENST00000674475.1 | c.909-422A>G | intron_variant | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.390 AC: 59317AN: 151916Hom.: 12020 Cov.: 32
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GnomAD3 exomes AF: 0.370 AC: 92957AN: 251182Hom.: 18713 AF XY: 0.372 AC XY: 50496AN XY: 135754
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GnomAD4 exome AF: 0.410 AC: 599913AN: 1461644Hom.: 127009 Cov.: 70 AF XY: 0.409 AC XY: 297101AN XY: 727090
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GnomAD4 genome ? AF: 0.390 AC: 59338AN: 152034Hom.: 12024 Cov.: 32 AF XY: 0.387 AC XY: 28793AN XY: 74308
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2019 | - - |
Computational scores
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Name
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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