rs3758371

Variant names:

• chr10-29564242-G-C
• rs3758371
• NM_021738.3:c.-142-950C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-29564242-G-C
• chr10-29564242-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021738.3(SVIL):​c.-142-950C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,004 control chromosomes in the GnomAD database, including 5,776 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 0.27 (5776 hom., cov: 32)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 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.-142-950C>G		intron	N/A	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.-142-950C>G		intron	N/A	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.-142-950C>G		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.-142-950C>G		intron	N/A	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.-142-950C>G		intron	N/A	ENSP00000364549.3	O95425-2
	SVIL	ENST00000860295.1		c.-142-950C>G		intron	N/A	ENSP00000530354.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41564 AN: 151886 Hom.: 5769 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41590 AN: 152004 Hom.: 5776 Cov.: 32 AF XY: 0.274 AC XY: 20358 AN XY: 74300

African (AFR) AF: 0.302 AC: 12512 AN: 41426

American (AMR) AF: 0.278 AC: 4250 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5156

South Asian (SAS) AF: 0.201 AC: 967 AN: 4820

European-Finnish (FIN) AF: 0.292 AC: 3086 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17498 AN: 67980

Other (OTH) AF: 0.254 AC: 535 AN: 2108

Alfa AF: 0.168 Hom.: 370

Bravo AF: 0.276

Asia WGS AF: 0.280 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.43
PhyloP100		0.95
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: rs3758371; hg19: chr10-29853171;