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rs1328323

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021738.3(SVIL):ā€‹c.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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04
Variant links:
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
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
SVILNM_021738.3 linkuse as main transcriptc.1773A>G p.Lys591= synonymous_variant 8/38 ENST00000355867.9
SVILNM_001323599.2 linkuse as main transcriptc.909-422A>G intron_variant
SVILNM_001323600.1 linkuse as main transcriptc.828-1306A>G intron_variant
SVILNM_003174.3 linkuse as main transcriptc.828-1306A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SVILENST00000355867.9 linkuse as main transcriptc.1773A>G p.Lys591= synonymous_variant 8/381 NM_021738.3 A2O95425-1
SVILENST00000375400.7 linkuse as main transcriptc.828-1306A>G intron_variant 1 P2O95425-2
SVILENST00000375398.6 linkuse as main transcriptc.1773A>G p.Lys591= synonymous_variant 8/375 A2O95425-4
SVILENST00000674475.1 linkuse as main transcriptc.909-422A>G intron_variant A2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.390
AC:
59317
AN:
151916
Hom.:
12020
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.347
Gnomad AMI
AF:
0.736
Gnomad AMR
AF:
0.371
Gnomad ASJ
AF:
0.351
Gnomad EAS
AF:
0.0808
Gnomad SAS
AF:
0.310
Gnomad FIN
AF:
0.444
Gnomad MID
AF:
0.361
Gnomad NFE
AF:
0.439
Gnomad OTH
AF:
0.394
GnomAD3 exomes
AF:
0.370
AC:
92957
AN:
251182
Hom.:
18713
AF XY:
0.372
AC XY:
50496
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.348
Gnomad AMR exome
AF:
0.282
Gnomad ASJ exome
AF:
0.356
Gnomad EAS exome
AF:
0.0847
Gnomad SAS exome
AF:
0.319
Gnomad FIN exome
AF:
0.454
Gnomad NFE exome
AF:
0.444
Gnomad OTH exome
AF:
0.394
GnomAD4 exome
AF:
0.410
AC:
599913
AN:
1461644
Hom.:
127009
Cov.:
70
AF XY:
0.409
AC XY:
297101
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.346
Gnomad4 AMR exome
AF:
0.294
Gnomad4 ASJ exome
AF:
0.352
Gnomad4 EAS exome
AF:
0.0789
Gnomad4 SAS exome
AF:
0.319
Gnomad4 FIN exome
AF:
0.455
Gnomad4 NFE exome
AF:
0.437
Gnomad4 OTH exome
AF:
0.383
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.390
AC:
59338
AN:
152034
Hom.:
12024
Cov.:
32
AF XY:
0.387
AC XY:
28793
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.347
Gnomad4 AMR
AF:
0.370
Gnomad4 ASJ
AF:
0.351
Gnomad4 EAS
AF:
0.0812
Gnomad4 SAS
AF:
0.310
Gnomad4 FIN
AF:
0.444
Gnomad4 NFE
AF:
0.439
Gnomad4 OTH
AF:
0.391
Alfa
AF:
0.413
Hom.:
9233
Bravo
AF:
0.382
Asia WGS
AF:
0.202
AC:
704
AN:
3478
EpiCase
AF:
0.441
EpiControl
AF:
0.432

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 submitterclinical testingGeneDxFeb 07, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
8.8
DANN
Benign
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1328323; hg19: chr10-29821523; COSMIC: COSV63444852; API