rs1270874

Variant names:

• chr10-29550935-A-C
• rs1270874
• NM_021738.3:c.489T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 23 publications found

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, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

SVIL-AS1 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021738.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	NM_021738.3	MANE Select	c.489T>G	p.Ala163Ala	synonymous	Exon 6 of 38	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.489T>G	p.Ala163Ala	synonymous	Exon 8 of 39	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.489T>G	p.Ala163Ala	synonymous	Exon 8 of 37	NP_001310529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.489T>G	p.Ala163Ala	synonymous	Exon 6 of 38	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.489T>G	p.Ala163Ala	synonymous	Exon 8 of 36	ENSP00000364549.3	O95425-2
	SVIL	ENST00000860295.1		c.489T>G	p.Ala163Ala	synonymous	Exon 6 of 40	ENSP00000530354.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108620 AN: 151696 Hom.: 38986 Cov.: 30

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

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

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

GnomAD4 genome AF: 0.716 AC: 108722 AN: 151814 Hom.: 39029 Cov.: 30 AF XY: 0.720 AC XY: 53359 AN XY: 74154

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

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 v4.9

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

Other links and lift over

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