chr10-29550935-A-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_021738.3(SVIL):​c.489T>G​(p.Ala163Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,613,692 control chromosomes in the GnomAD database, including 436,481 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 0.72 ( 39029 hom., cov: 30)
Exomes 𝑓: 0.74 ( 397452 hom. )

Consequence

SVIL
NM_021738.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

23 publications found
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 Gene-Disease associations (from GenCC):
  • myofibrillar myopathy 10
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP7
Synonymous conserved (PhyloP=-1.58 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SVILNM_021738.3 linkc.489T>G p.Ala163Ala synonymous_variant Exon 6 of 38 ENST00000355867.9 NP_068506.2 O95425-1Q569J5
SVILNM_001323599.2 linkc.489T>G p.Ala163Ala synonymous_variant Exon 8 of 39 NP_001310528.1 A0A6I8PIX7
SVILNM_001323600.1 linkc.489T>G p.Ala163Ala synonymous_variant Exon 8 of 37 NP_001310529.1
SVILNM_003174.3 linkc.489T>G p.Ala163Ala synonymous_variant Exon 8 of 36 NP_003165.2 O95425-2Q569J5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SVILENST00000355867.9 linkc.489T>G p.Ala163Ala synonymous_variant Exon 6 of 38 1 NM_021738.3 ENSP00000348128.4 O95425-1

Frequencies

GnomAD3 genomes
AF:
0.716
AC:
108620
AN:
151696
Hom.:
38986
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.662
Gnomad AMI
AF:
0.774
Gnomad AMR
AF:
0.719
Gnomad ASJ
AF:
0.617
Gnomad EAS
AF:
0.836
Gnomad SAS
AF:
0.765
Gnomad FIN
AF:
0.776
Gnomad MID
AF:
0.634
Gnomad NFE
AF:
0.731
Gnomad OTH
AF:
0.696
GnomAD2 exomes
AF:
0.735
AC:
184795
AN:
251448
AF XY:
0.735
show subpopulations
Gnomad AFR exome
AF:
0.659
Gnomad AMR exome
AF:
0.722
Gnomad ASJ exome
AF:
0.616
Gnomad EAS exome
AF:
0.830
Gnomad FIN exome
AF:
0.775
Gnomad NFE exome
AF:
0.730
Gnomad OTH exome
AF:
0.709
GnomAD4 exome
AF:
0.736
AC:
1076298
AN:
1461878
Hom.:
397452
Cov.:
86
AF XY:
0.737
AC XY:
535948
AN XY:
727238
show subpopulations
African (AFR)
AF:
0.656
AC:
21962
AN:
33480
American (AMR)
AF:
0.718
AC:
32113
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.620
AC:
16210
AN:
26136
East Asian (EAS)
AF:
0.848
AC:
33651
AN:
39700
South Asian (SAS)
AF:
0.766
AC:
66099
AN:
86258
European-Finnish (FIN)
AF:
0.776
AC:
41473
AN:
53418
Middle Eastern (MID)
AF:
0.631
AC:
3637
AN:
5768
European-Non Finnish (NFE)
AF:
0.735
AC:
817701
AN:
1112000
Other (OTH)
AF:
0.719
AC:
43452
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
19881
39762
59642
79523
99404
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20118
40236
60354
80472
100590
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.716
AC:
108722
AN:
151814
Hom.:
39029
Cov.:
30
AF XY:
0.720
AC XY:
53359
AN XY:
74154
show subpopulations
African (AFR)
AF:
0.663
AC:
27424
AN:
41394
American (AMR)
AF:
0.720
AC:
11004
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.617
AC:
2136
AN:
3464
East Asian (EAS)
AF:
0.836
AC:
4276
AN:
5116
South Asian (SAS)
AF:
0.766
AC:
3665
AN:
4784
European-Finnish (FIN)
AF:
0.776
AC:
8168
AN:
10528
Middle Eastern (MID)
AF:
0.630
AC:
184
AN:
292
European-Non Finnish (NFE)
AF:
0.731
AC:
49688
AN:
67934
Other (OTH)
AF:
0.698
AC:
1471
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1560
3120
4681
6241
7801
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
844
1688
2532
3376
4220
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.725
Hom.:
108505
Bravo
AF:
0.709
Asia WGS
AF:
0.784
AC:
2724
AN:
3478
EpiCase
AF:
0.723
EpiControl
AF:
0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.44
DANN
Benign
0.37
PhyloP100
-1.6
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1270874; hg19: chr10-29839864; COSMIC: COSV63446677; COSMIC: COSV63446677; API