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GeneBe

10-29458292-G-A

Variant summary

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

The NM_021738.3(SVIL):c.6600C>T(p.Pro2200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,960 control chromosomes in the GnomAD database, including 11,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.095 ( 869 hom., cov: 33)
Exomes 𝑓: 0.12 ( 10976 hom. )

Consequence

SVIL
NM_021738.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23
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]
SVIL-AS1 (HGNC:51219): (SVIL antisense RNA 1)

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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=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-29458292-G-A is Benign according to our data. Variant chr10-29458292-G-A is described in ClinVar as [Benign]. Clinvar id is 1225817.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=-1.23 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 = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SVILNM_021738.3 linkuse as main transcriptc.6600C>T p.Pro2200= synonymous_variant 38/38 ENST00000355867.9
SVIL-AS1NR_110927.1 linkuse as main transcriptn.182-28863G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SVILENST00000355867.9 linkuse as main transcriptc.6600C>T p.Pro2200= synonymous_variant 38/381 NM_021738.3 A2O95425-1
SVIL-AS1ENST00000684815.1 linkuse as main transcriptn.236+42880G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0950
AC:
14441
AN:
152058
Hom.:
870
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0467
Gnomad AMI
AF:
0.163
Gnomad AMR
AF:
0.0849
Gnomad ASJ
AF:
0.0504
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0292
Gnomad FIN
AF:
0.146
Gnomad MID
AF:
0.0510
Gnomad NFE
AF:
0.132
Gnomad OTH
AF:
0.0875
GnomAD3 exomes
AF:
0.0889
AC:
22350
AN:
251368
Hom.:
1352
AF XY:
0.0885
AC XY:
12029
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0468
Gnomad AMR exome
AF:
0.0461
Gnomad ASJ exome
AF:
0.0555
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.0319
Gnomad FIN exome
AF:
0.152
Gnomad NFE exome
AF:
0.128
Gnomad OTH exome
AF:
0.0925
GnomAD4 exome
AF:
0.116
AC:
169418
AN:
1461784
Hom.:
10976
Cov.:
31
AF XY:
0.113
AC XY:
82453
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.0457
Gnomad4 AMR exome
AF:
0.0486
Gnomad4 ASJ exome
AF:
0.0548
Gnomad4 EAS exome
AF:
0.000252
Gnomad4 SAS exome
AF:
0.0317
Gnomad4 FIN exome
AF:
0.153
Gnomad4 NFE exome
AF:
0.132
Gnomad4 OTH exome
AF:
0.103
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0949
AC:
14438
AN:
152176
Hom.:
869
Cov.:
33
AF XY:
0.0956
AC XY:
7109
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0466
Gnomad4 AMR
AF:
0.0848
Gnomad4 ASJ
AF:
0.0504
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.0290
Gnomad4 FIN
AF:
0.146
Gnomad4 NFE
AF:
0.132
Gnomad4 OTH
AF:
0.0866
Alfa
AF:
0.111
Hom.:
532
Bravo
AF:
0.0881
Asia WGS
AF:
0.0190
AC:
68
AN:
3478
EpiCase
AF:
0.120
EpiControl
AF:
0.112

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 testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
2.3
Dann
Benign
0.85

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: rs41299212; hg19: chr10-29747221; COSMIC: COSV63439978; API