rs17756919

Variant names:

• chr10-29532160-C-T
• rs17756919
• NM_021738.3:c.1851G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021738.3(SVIL):​c.1851G>A​(p.Val617Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,406 control chromosomes in the GnomAD database, including 119,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10590 hom., cov: 33)
  • Exomes 𝑓: 0.38 (108896 hom.)
• Consequence: SVIL NM_021738.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.31
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-29532160-C-T is Benign according to our data. Variant chr10-29532160-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 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.1851G>A	p.Val617Val	synonymous	Exon 9 of 38	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.921G>A	p.Val307Val	synonymous	Exon 10 of 39	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.828-872G>A		intron	N/A	NP_001310529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.1851G>A	p.Val617Val	synonymous	Exon 9 of 38	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.828-872G>A		intron	N/A	ENSP00000364549.3	O95425-2
	SVIL	ENST00000860295.1		c.1851G>A	p.Val617Val	synonymous	Exon 9 of 40	ENSP00000530354.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55868 AN: 151976 Hom.: 10587 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.0806

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.346 AC: 86665 AN: 250812 AF XY: 0.347

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.0848

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.407

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.381 AC: 556056 AN: 1461312 Hom.: 108896 Cov.: 48 AF XY: 0.379 AC XY: 275469 AN XY: 726972

African (AFR) AF: 0.341 AC: 11422 AN: 33460

American (AMR) AF: 0.281 AC: 12552 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 8343 AN: 26126

East Asian (EAS) AF: 0.0789 AC: 3133 AN: 39698

South Asian (SAS) AF: 0.309 AC: 26637 AN: 86230

European-Finnish (FIN) AF: 0.421 AC: 22452 AN: 53386

Middle Eastern (MID) AF: 0.322 AC: 1836 AN: 5706

European-Non Finnish (NFE) AF: 0.403 AC: 448137 AN: 1111664

Other (OTH) AF: 0.357 AC: 21544 AN: 60352

GnomAD4 genome AF: 0.367 AC: 55887 AN: 152094 Hom.: 10590 Cov.: 33 AF XY: 0.365 AC XY: 27157 AN XY: 74350

African (AFR) AF: 0.341 AC: 14141 AN: 41486

American (AMR) AF: 0.349 AC: 5331 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3466

East Asian (EAS) AF: 0.0810 AC: 419 AN: 5176

South Asian (SAS) AF: 0.301 AC: 1449 AN: 4820

European-Finnish (FIN) AF: 0.415 AC: 4392 AN: 10580

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27562 AN: 67970

Other (OTH) AF: 0.370 AC: 781 AN: 2110

Alfa AF: 0.386 Hom.: 38261

Bravo AF: 0.360

Asia WGS AF: 0.197 AC: 689 AN: 3478

EpiCase AF: 0.408

EpiControl AF: 0.398

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		1.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs17756919; hg19: chr10-29821089;